Nutrient chapter

Vitamin K2 / menaquinone family

Vitamin K2 is a family of menaquinones, including MK-4 and MK-7. These forms participate in the shared vitamin K cycle but differ in synthesis, exposure and studied effects.

99 recorded mechanisms · 16 availability situations · 4 preserved sources. Draft and verified records are labeled separately.

Read recorded mechanisms Open recursive mind map

The mechanisms

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

GGCX couples oxidation of reduced vitamin K to conversion of protein-bound glutamate into gamma-carboxyglutamate.
Gamma-glutamyl carboxylase / GGCX → Reduced vitamin K hydroquinone family source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/39880952.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "eb8e6d00eecd7c5c780921cae3f804fab60e919301eeb16e9909f36293aaa653", "start_char": 0, "end_char": 1230, "text_sha256": "eb8e6d00eecd7c5c780921cae3f804fab60e919301eeb16e9909f36293aaa653"}
experimental_model
Cryo-EM, binding, cell assays and molecular dynamics
exposure
Apo, osteocalcin-bound and vitamin-K-bound structures
limitations
Shared vitamin K chemistry; the abstract does not establish K2 exclusivity or identical kinetics for every menaquinone.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Human GGCX
plain_language
Vitamin K helps an enzyme modify selected proteins; it does not carry calcium into bone itself.
primary_references
[k2-p39880952] Structure and mechanism of vitamin-K-dependent γ-glutamyl carboxylase. (2025). https://pubmed.ncbi.nlm.nih.gov/39880952/ DOI: 10.1038/s41586-024-08484-9
tissue_or_cell_type
Endoplasmic-reticulum membrane enzyme
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 370–381
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cryo-EM, binding, cell assays and molecular dynamics · source_derived_draft · unverified_draft
### k2-ggcx-cofactor GGCX couples oxidation of reduced vitamin K to conversion of protein-bound glutamate into gamma-carboxyglutamate. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin K helps an enzyme modify selected proteins; it does not carry calcium into bone itself. organism: Human GGCX tissue_or_cell_type: Endoplasmic-reticulum membrane enzyme experimental_model: Cryo-EM, binding, cell assays and molecular dynamics limitations: Shared vitamin K chemistry; the abstract does not establish K2 exclusivity or identical kinetics for every menaquinone. exposure: Apo, osteocalcin-bound and vitamin-K-bound structures evidence_span: {"source_cache": "artifacts/k2-research/39880952.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "eb8e6d00eecd7c5c780921cae3f804fab60e919301eeb16e9909f36293aaa653", "start_char": 0, "end_char": 1230, "text_sha256": "eb8e6d00eecd7c5c780921cae3f804fab60e919301eeb16e9909f36293aaa653"} [k2-p39880952] Structure and mechanism of vitamin-K-dependent γ-glutamyl carboxylase. (2025). https://pubmed.ncbi.nlm.nih.gov/39880952/ DOI: 10.1038/s41586-024-08484-9
Complete structured claim and evidence
Silencing the identified VKORC1 gene reduced vitamin K epoxide reductase activity; recombinant expression restored warfarin-sensitive enzyme activity.
Human vitamin K epoxide reductase / VKORC1 → Vitamin K epoxide recycling source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/14765195.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "32f373fc0363ed079e580b2d47a3cb36c82b46871860fc6740b0285e23936496", "start_char": 0, "end_char": 1385, "text_sha256": "32f373fc0363ed079e580b2d47a3cb36c82b46871860fc6740b0285e23936496"}
experimental_model
siRNA identification and recombinant expression
exposure
Gene silencing, enzyme expression and warfarin sensitivity
limitations
Gene-discovery experiments; later structural understanding supersedes the original minimal topology description.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Human VKORC1 and insect-cell expression
plain_language
The used vitamin K cofactor can be recycled instead of being replaced after every reaction.
primary_references
[k2-p14765195] Identification of the gene for vitamin K epoxide reductase. (2004). https://pubmed.ncbi.nlm.nih.gov/14765195/ DOI: 10.1038/nature02254
tissue_or_cell_type
Vitamin K recycling enzyme
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 435–446
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · siRNA identification and recombinant expression · source_derived_draft · unverified_draft
### k2-vkor-recycling Silencing the identified VKORC1 gene reduced vitamin K epoxide reductase activity; recombinant expression restored warfarin-sensitive enzyme activity. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The used vitamin K cofactor can be recycled instead of being replaced after every reaction. organism: Human VKORC1 and insect-cell expression tissue_or_cell_type: Vitamin K recycling enzyme experimental_model: siRNA identification and recombinant expression limitations: Gene-discovery experiments; later structural understanding supersedes the original minimal topology description. exposure: Gene silencing, enzyme expression and warfarin sensitivity evidence_span: {"source_cache": "artifacts/k2-research/14765195.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "32f373fc0363ed079e580b2d47a3cb36c82b46871860fc6740b0285e23936496", "start_char": 0, "end_char": 1385, "text_sha256": "32f373fc0363ed079e580b2d47a3cb36c82b46871860fc6740b0285e23936496"} [k2-p14765195] Identification of the gene for vitamin K epoxide reductase. (2004). https://pubmed.ncbi.nlm.nih.gov/14765195/ DOI: 10.1038/nature02254
Complete structured claim and evidence
Human UBIAD1 expression supported conversion of labeled vitamin K precursors to MK-4, identified by deuterium NMR.
Human UBIAD1 prenyltransferase → Menaquinone-4 biosynthesis source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/20953171.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b8786e664d3b32db7b0cca72c710e24f1546e14f0a69c031908400731174cea3", "start_char": 0, "end_char": 2006, "text_sha256": "b8786e664d3b32db7b0cca72c710e24f1546e14f0a69c031908400731174cea3"}
experimental_model
Gene knockdown, heterologous expression, isotope conversion and NMR
exposure
Labeled vitamin K precursors, UBIAD1 knockdown and expression
limitations
Identifies a biosynthetic enzyme, not a clinical requirement to supplement MK-4. K1-derived MK-4 synthesis does not make humans independent of external vitamin K precursors.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Human UBIAD1 in human and insect-cell systems; mouse localization
plain_language
Cells have an enzyme that can make MK-4 from vitamin K precursors.
primary_references
[k2-p20953171] Identification of UBIAD1 as a novel human menaquinone-4 biosynthetic enzyme. (2010). https://pubmed.ncbi.nlm.nih.gov/20953171/ DOI: 10.1038/nature09464
tissue_or_cell_type
MK-4 synthesis
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 136–147
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Gene knockdown, heterologous expression, isotope conversion and NMR · source_derived_draft · unverified_draft
### k2-ubiad1-synthesis Human UBIAD1 expression supported conversion of labeled vitamin K precursors to MK-4, identified by deuterium NMR. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Cells have an enzyme that can make MK-4 from vitamin K precursors. organism: Human UBIAD1 in human and insect-cell systems; mouse localization tissue_or_cell_type: MK-4 synthesis experimental_model: Gene knockdown, heterologous expression, isotope conversion and NMR limitations: Identifies a biosynthetic enzyme, not a clinical requirement to supplement MK-4. K1-derived MK-4 synthesis does not make humans independent of external vitamin K precursors. exposure: Labeled vitamin K precursors, UBIAD1 knockdown and expression evidence_span: {"source_cache": "artifacts/k2-research/20953171.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b8786e664d3b32db7b0cca72c710e24f1546e14f0a69c031908400731174cea3", "start_char": 0, "end_char": 2006, "text_sha256": "b8786e664d3b32db7b0cca72c710e24f1546e14f0a69c031908400731174cea3"} [k2-p20953171] Identification of UBIAD1 as a novel human menaquinone-4 biosynthetic enzyme. (2010). https://pubmed.ncbi.nlm.nih.gov/20953171/ DOI: 10.1038/nature09464
Complete structured claim and evidence
MK-7 showed more stable serum levels and seven- to eightfold higher accumulation during repeated intake than K1 in the comparison.
Menaquinone-7 / MK-7 → Phylloquinone source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/17158229.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1bf2196600220143fbc5ba85e8aba71b4c8aa931f4a6c47545c3db9570283faf", "start_char": 0, "end_char": 1248, "text_sha256": "1bf2196600220143fbc5ba85e8aba71b4c8aa931f4a6c47545c3db9570283faf"}
experimental_model
Comparative human absorption and activity experiments
exposure
Phylloquinone versus natto-derived MK-7
limitations
Biochemical exposure and activity endpoints, not fracture or cardiovascular-event prevention.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Healthy volunteers
plain_language
Different vitamin K forms have different blood-exposure profiles.
primary_references
[k2-p17158229] Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7. (2007). https://pubmed.ncbi.nlm.nih.gov/17158229/ DOI: 10.1182/blood-2006-08-040709
tissue_or_cell_type
Serum vitamers and osteocalcin
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 292–303
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Comparative human absorption and activity experiments · source_derived_draft · unverified_draft
### k2-mk7-persistence MK-7 showed more stable serum levels and seven- to eightfold higher accumulation during repeated intake than K1 in the comparison. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Different vitamin K forms have different blood-exposure profiles. organism: Healthy volunteers tissue_or_cell_type: Serum vitamers and osteocalcin experimental_model: Comparative human absorption and activity experiments limitations: Biochemical exposure and activity endpoints, not fracture or cardiovascular-event prevention. exposure: Phylloquinone versus natto-derived MK-7 evidence_span: {"source_cache": "artifacts/k2-research/17158229.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1bf2196600220143fbc5ba85e8aba71b4c8aa931f4a6c47545c3db9570283faf", "start_char": 0, "end_char": 1248, "text_sha256": "1bf2196600220143fbc5ba85e8aba71b4c8aa931f4a6c47545c3db9570283faf"} [k2-p17158229] Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7. (2007). https://pubmed.ncbi.nlm.nih.gov/17158229/ DOI: 10.1182/blood-2006-08-040709
Complete structured claim and evidence
Full-length MGP and its gamma-carboxylated domain inhibited calcium deposition in the tested vascular-cell model.
Gamma-carboxylated matrix Gla protein → Vascular smooth muscle cell matrix calcification source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/17848178.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d2d79c43cc8142d6dc8f1eab4ac99b05ceb01e50e5afb41f5ca75aec732cba27", "start_char": 0, "end_char": 1745, "text_sha256": "d2d79c43cc8142d6dc8f1eab4ac99b05ceb01e50e5afb41f5ca75aec732cba27"}
experimental_model
Human vascular-cell calcification and synthetic-peptide assays
exposure
Elevated calcium, warfarin, K1 and modified MGP peptides
limitations
Vitamin K1 intervention in cells; K2-specific efficacy and human arterial reversal were not tested.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Human vascular smooth muscle cells
plain_language
One vitamin K-dependent protein modification contributes to local control of mineral deposition.
primary_references
[k2-p17848178] Post-translational modifications regulate matrix Gla protein function: importance for inhibition of vascular smooth muscle cell calcification. (2007). https://pubmed.ncbi.nlm.nih.gov/17848178/ DOI: 10.1111/j.1538-7836.2007.02758.x
tissue_or_cell_type
Extracellular matrix and vesicle-like surfaces
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 513–524
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human vascular-cell calcification and synthetic-peptide assays · source_derived_draft · unverified_draft
### k2-mgp-gla Full-length MGP and its gamma-carboxylated domain inhibited calcium deposition in the tested vascular-cell model. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: One vitamin K-dependent protein modification contributes to local control of mineral deposition. organism: Human vascular smooth muscle cells tissue_or_cell_type: Extracellular matrix and vesicle-like surfaces experimental_model: Human vascular-cell calcification and synthetic-peptide assays limitations: Vitamin K1 intervention in cells; K2-specific efficacy and human arterial reversal were not tested. exposure: Elevated calcium, warfarin, K1 and modified MGP peptides evidence_span: {"source_cache": "artifacts/k2-research/17848178.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d2d79c43cc8142d6dc8f1eab4ac99b05ceb01e50e5afb41f5ca75aec732cba27", "start_char": 0, "end_char": 1745, "text_sha256": "d2d79c43cc8142d6dc8f1eab4ac99b05ceb01e50e5afb41f5ca75aec732cba27"} [k2-p17848178] Post-translational modifications regulate matrix Gla protein function: importance for inhibition of vascular smooth muscle cell calcification. (2007). https://pubmed.ncbi.nlm.nih.gov/17848178/ DOI: 10.1111/j.1538-7836.2007.02758.x
Complete structured claim and evidence
Deleting Bglap and Bglap2 disrupted apatite-crystal orientation relative to collagen while collagen orientation and crystal size remained normal.
Mouse osteocalcin / Bglap → Alignment of bone apatite crystals with collagen source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/k2-research/32463816.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "287e43177fb9d632a2cba982f851b0a5a99d469761a1b2ad1e9e9e26933f850a", "start_char": 0, "end_char": 1082, "text_sha256": "287e43177fb9d632a2cba982f851b0a5a99d469761a1b2ad1e9e9e26933f850a"}
experimental_model
Bglap/Bglap2 double-deletion and skeletal analysis
exposure
Osteocalcin loss
limitations
Protein deletion rather than K2 restriction; endocrine findings in this mouse line cannot settle all osteocalcin hormone claims.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Mice
plain_language
Having mineral present did not guarantee that it was organized correctly.
primary_references
[k2-p32463816] Osteocalcin is necessary for the alignment of apatite crystallites, but not glucose metabolism, testosterone synthesis, or muscle mass. (2020). https://pubmed.ncbi.nlm.nih.gov/32463816/ DOI: 10.1371/journal.pgen.1008586
tissue_or_cell_type
Bone mineral orientation and mechanical properties
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 487–498
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Bglap/Bglap2 double-deletion and skeletal analysis · source_derived_draft · unverified_draft
### k2-osteocalcin-alignment Deleting Bglap and Bglap2 disrupted apatite-crystal orientation relative to collagen while collagen orientation and crystal size remained normal. Condition category: machinery_impairment nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Having mineral present did not guarantee that it was organized correctly. organism: Mice tissue_or_cell_type: Bone mineral orientation and mechanical properties experimental_model: Bglap/Bglap2 double-deletion and skeletal analysis limitations: Protein deletion rather than K2 restriction; endocrine findings in this mouse line cannot settle all osteocalcin hormone claims. exposure: Osteocalcin loss evidence_span: {"source_cache": "artifacts/k2-research/32463816.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "287e43177fb9d632a2cba982f851b0a5a99d469761a1b2ad1e9e9e26933f850a", "start_char": 0, "end_char": 1082, "text_sha256": "287e43177fb9d632a2cba982f851b0a5a99d469761a1b2ad1e9e9e26933f850a"} [k2-p32463816] Osteocalcin is necessary for the alignment of apatite crystallites, but not glucose metabolism, testosterone synthesis, or muscle mass. (2020). https://pubmed.ncbi.nlm.nih.gov/32463816/ DOI: 10.1371/journal.pgen.1008586
Complete structured claim and evidence
Recombinant carboxylated GAS6 increased precursor fusion, osteoclast size and nuclei per osteoclast in culture.
Gamma-carboxylated mouse GAS6 → Fusion of osteoclast precursors source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/42045170.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "590b559787319a57a3e2fae4164fc2f2a40761ce653bd426d34a2d76aff5d4cf", "start_char": 0, "end_char": 1703, "text_sha256": "590b559787319a57a3e2fae4164fc2f2a40761ce653bd426d34a2d76aff5d4cf"}
experimental_model
Osteoblast-specific deletion, co-culture, receptor inhibitors and transgenic overexpression
exposure
Osteoblast Ggcx deletion; carboxylated GAS6 and AXL/MERTK perturbation
limitations
2026 mouse study; increased bone mass is not proven improved human bone quality, and no oral MK-7 regimen was tested.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Male mice and mouse osteoblast/osteoclast cultures
plain_language
One modified protein helps bone-resorbing cells mature.
primary_references
[k2-p42045170] Vitamin K-dependent carboxylation in osteoblasts regulates bone resorption through GAS6 in male mice. (2026). https://pubmed.ncbi.nlm.nih.gov/42045170/ DOI: 10.1038/s41413-026-00528-2
tissue_or_cell_type
Bone remodeling
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 643–654
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Osteoblast-specific deletion, co-culture, receptor inhibitors and transgenic overexpression · source_derived_draft · unverified_draft
### k2-gas6-fusion Recombinant carboxylated GAS6 increased precursor fusion, osteoclast size and nuclei per osteoclast in culture. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: One modified protein helps bone-resorbing cells mature. organism: Male mice and mouse osteoblast/osteoclast cultures tissue_or_cell_type: Bone remodeling experimental_model: Osteoblast-specific deletion, co-culture, receptor inhibitors and transgenic overexpression limitations: 2026 mouse study; increased bone mass is not proven improved human bone quality, and no oral MK-7 regimen was tested. exposure: Osteoblast Ggcx deletion; carboxylated GAS6 and AXL/MERTK perturbation evidence_span: {"source_cache": "artifacts/k2-research/42045170.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "590b559787319a57a3e2fae4164fc2f2a40761ce653bd426d34a2d76aff5d4cf", "start_char": 0, "end_char": 1703, "text_sha256": "590b559787319a57a3e2fae4164fc2f2a40761ce653bd426d34a2d76aff5d4cf"} [k2-p42045170] Vitamin K-dependent carboxylation in osteoblasts regulates bone resorption through GAS6 in male mice. (2026). https://pubmed.ncbi.nlm.nih.gov/42045170/ DOI: 10.1038/s41413-026-00528-2
Complete structured claim and evidence
FSP1 reduced vitamin K quinones to radical-trapping hydroquinones using NAD(P)H.
FSP1 / AIFM2 → Reduced vitamin K hydroquinone family source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/35922516.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3bd5750fd2d12a754ad4237018851391c6b5b80bac6ad58307321fb7c3042c5a", "start_char": 0, "end_char": 1403, "text_sha256": "3bd5750fd2d12a754ad4237018851391c6b5b80bac6ad58307321fb7c3042c5a"}
experimental_model
Enzyme/liposome chemistry, knockout cells and warfarin-exposed mice
exposure
MK-4/K1, NAD(P)H, FSP1 loss and inhibitors
limitations
Preclinical experiments; not a demonstrated oral MK-7 treatment for ferroptosis-related disease or a self-treatment regimen for anticoagulant poisoning.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Human recombinant FSP1, mammalian cells and mice
plain_language
A niacin-derived electron donor helps regenerate the reduced antioxidant form.
primary_references
[k2-p35922516] A non-canonical vitamin K cycle is a potent ferroptosis suppressor. (2022). https://pubmed.ncbi.nlm.nih.gov/35922516/ DOI: 10.1038/s41586-022-05022-3
tissue_or_cell_type
Lipid peroxidation and vitamin K reduction
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 773–784
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Enzyme/liposome chemistry, knockout cells and warfarin-exposed mice · source_derived_draft · unverified_draft
### k2-fsp1-k-reduction FSP1 reduced vitamin K quinones to radical-trapping hydroquinones using NAD(P)H. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A niacin-derived electron donor helps regenerate the reduced antioxidant form. organism: Human recombinant FSP1, mammalian cells and mice tissue_or_cell_type: Lipid peroxidation and vitamin K reduction experimental_model: Enzyme/liposome chemistry, knockout cells and warfarin-exposed mice limitations: Preclinical experiments; not a demonstrated oral MK-7 treatment for ferroptosis-related disease or a self-treatment regimen for anticoagulant poisoning. exposure: MK-4/K1, NAD(P)H, FSP1 loss and inhibitors evidence_span: {"source_cache": "artifacts/k2-research/35922516.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3bd5750fd2d12a754ad4237018851391c6b5b80bac6ad58307321fb7c3042c5a", "start_char": 0, "end_char": 1403, "text_sha256": "3bd5750fd2d12a754ad4237018851391c6b5b80bac6ad58307321fb7c3042c5a"} [k2-p35922516] A non-canonical vitamin K cycle is a potent ferroptosis suppressor. (2022). https://pubmed.ncbi.nlm.nih.gov/35922516/ DOI: 10.1038/s41586-022-05022-3
Complete structured claim and evidence
Dietary K1 restriction reduced prothrombin and osteocalcin gamma-carboxylation and lowered plasma K1 and urinary Gla excretion.
Phylloquinone → Vitamin K-dependent protein gamma-carboxylation source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/k2-research/12888638.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c57beda0b2c7bdc471fd6f4bfa926e9f12846f040c95689648f599d6cceae874", "start_char": 0, "end_char": 1461, "text_sha256": "c57beda0b2c7bdc471fd6f4bfa926e9f12846f040c95689648f599d6cceae874"}
experimental_model
Metabolic-unit dietary depletion/repletion
exposure
K1 restricted to 18 micrograms/day for 28 days, then stepped repletion
limitations
The measured endpoint is carboxylation, not an observed clinical clotting failure; restricted-K1 exposure does not define isolated K2 deficiency.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
21 women aged 60–80 years
plain_language
A shortfall can appear in protein-modification markers before it is described as a clinical syndrome.
primary_references
[k2-p12888638] Dietary phylloquinone depletion and repletion in older women. (2003). https://pubmed.ncbi.nlm.nih.gov/12888638/ DOI: 10.1093/jn/133.8.2565
tissue_or_cell_type
Hepatic and extrahepatic protein markers
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 1007–1018
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Metabolic-unit dietary depletion/repletion · source_derived_draft · unverified_draft
### k2-dietary-k-prothrombin Dietary K1 restriction reduced prothrombin and osteocalcin gamma-carboxylation and lowered plasma K1 and urinary Gla excretion. Condition category: nutrient_deficiency nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A shortfall can appear in protein-modification markers before it is described as a clinical syndrome. organism: 21 women aged 60–80 years tissue_or_cell_type: Hepatic and extrahepatic protein markers experimental_model: Metabolic-unit dietary depletion/repletion limitations: The measured endpoint is carboxylation, not an observed clinical clotting failure; restricted-K1 exposure does not define isolated K2 deficiency. exposure: K1 restricted to 18 micrograms/day for 28 days, then stepped repletion evidence_span: {"source_cache": "artifacts/k2-research/12888638.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c57beda0b2c7bdc471fd6f4bfa926e9f12846f040c95689648f599d6cceae874", "start_char": 0, "end_char": 1461, "text_sha256": "c57beda0b2c7bdc471fd6f4bfa926e9f12846f040c95689648f599d6cceae874"} [k2-p12888638] Dietary phylloquinone depletion and repletion in older women. (2003). https://pubmed.ncbi.nlm.nih.gov/12888638/ DOI: 10.1093/jn/133.8.2565
Complete structured claim and evidence
MK-7 at 45 micrograms/day lowered mean INR and uncarboxylated factor II by about 40%; lower doses altered anticoagulation in some participants.
Menaquinone-7 / MK-7 → International normalized ratio / INR source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/k2-research/23530987.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "95455ea6f2fc6de10ed4d46cad9c1587c004ccd445d7b08066108261f161e6af", "start_char": 0, "end_char": 1740, "text_sha256": "95455ea6f2fc6de10ed4d46cad9c1587c004ccd445d7b08066108261f161e6af"}
experimental_model
Sequential dose-response intervention during anticoagulation
exposure
Acenocoumarol followed by MK-7 10, 20 and 45 micrograms/day
limitations
Small pharmacological study; no dose here is a recommended safe self-adjustment. Drug was acenocoumarol, not warfarin.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
18 healthy adults; 15 attained target INR
plain_language
K2 is involved in clotting as well as extrahepatic functions.
primary_references
[k2-p23530987] Effect of low-dose supplements of menaquinone-7 (vitamin K2 ) on the stability of oral anticoagulant treatment: dose-response relationship in healthy volunteers. (2013). https://pubmed.ncbi.nlm.nih.gov/23530987/ DOI: 10.1111/jth.12203
tissue_or_cell_type
Coagulation, osteocalcin and MGP markers
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 1046–1057
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Sequential dose-response intervention during anticoagulation · source_derived_draft · unverified_draft
### k2-mk7-inr MK-7 at 45 micrograms/day lowered mean INR and uncarboxylated factor II by about 40%; lower doses altered anticoagulation in some participants. Condition category: machinery_impairment nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: K2 is involved in clotting as well as extrahepatic functions. organism: 18 healthy adults; 15 attained target INR tissue_or_cell_type: Coagulation, osteocalcin and MGP markers experimental_model: Sequential dose-response intervention during anticoagulation limitations: Small pharmacological study; no dose here is a recommended safe self-adjustment. Drug was acenocoumarol, not warfarin. exposure: Acenocoumarol followed by MK-7 10, 20 and 45 micrograms/day evidence_span: {"source_cache": "artifacts/k2-research/23530987.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "95455ea6f2fc6de10ed4d46cad9c1587c004ccd445d7b08066108261f161e6af", "start_char": 0, "end_char": 1740, "text_sha256": "95455ea6f2fc6de10ed4d46cad9c1587c004ccd445d7b08066108261f161e6af"} [k2-p23530987] Effect of low-dose supplements of menaquinone-7 (vitamin K2 ) on the stability of oral anticoagulant treatment: dose-response relationship in healthy volunteers. (2013). https://pubmed.ncbi.nlm.nih.gov/23530987/ DOI: 10.1111/jth.12203
Complete structured claim and evidence
After three years, BMD declined without significant between-group differences, and microarchitecture and turnover changes were also similar.
Menaquinone-7 / MK-7 → Bone mineral density source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Median CAC rose from 135 to 184 with MK-7 and from 145 to 214 with placebo over two years; adjusted group trajectories differed (P=0.02).
Menaquinone-7 / MK-7 → CT coronary artery calcium score source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/42268593.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8bd6d3cb0722f549b8a9c8f06feba3165dfd421c4ce0658b75b90a6e64e84a4b", "start_char": 0, "end_char": 2890, "text_sha256": "8bd6d3cb0722f549b8a9c8f06feba3165dfd421c4ce0658b75b90a6e64e84a4b"}
experimental_model
Two-year randomized placebo-controlled VitaK-CAC trial
exposure
MK-7 360 micrograms/day; baseline CAC 50–400
limitations
Published 2026; imaging surrogate, not demonstrated fewer infarctions, improved plaque stability or arterial calcium removal. One author disclosed grants from Gnosis and shares in Coagulation Profile outside this work.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
180 randomized symptomatic coronary-disease patients; 85 received MK-7 and 82 placebo
plain_language
Calcification still increased in both groups, but progressed more slowly with MK-7 in this trial.
primary_references
[k2-p42268593] Two Years of Menaquinone-7 Supplementation and Coronary Artery Calcification: A Randomized Clinical Trial. (2026). https://pubmed.ncbi.nlm.nih.gov/42268593/ DOI: 10.1001/jamacardio.2026.1279
tissue_or_cell_type
Coronary CT calcium score and calcium mass
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 1228–1239
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two-year randomized placebo-controlled VitaK-CAC trial · source_derived_draft · unverified_draft
### k2-vitak-cac Median CAC rose from 135 to 184 with MK-7 and from 145 to 214 with placebo over two years; adjusted group trajectories differed (P=0.02). Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Calcification still increased in both groups, but progressed more slowly with MK-7 in this trial. organism: 180 randomized symptomatic coronary-disease patients; 85 received MK-7 and 82 placebo tissue_or_cell_type: Coronary CT calcium score and calcium mass experimental_model: Two-year randomized placebo-controlled VitaK-CAC trial limitations: Published 2026; imaging surrogate, not demonstrated fewer infarctions, improved plaque stability or arterial calcium removal. One author disclosed grants from Gnosis and shares in Coagulation Profile outside this work. exposure: MK-7 360 micrograms/day; baseline CAC 50–400 evidence_span: {"source_cache": "artifacts/k2-research/42268593.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8bd6d3cb0722f549b8a9c8f06feba3165dfd421c4ce0658b75b90a6e64e84a4b", "start_char": 0, "end_char": 2890, "text_sha256": "8bd6d3cb0722f549b8a9c8f06feba3165dfd421c4ce0658b75b90a6e64e84a4b"} [k2-p42268593] Two Years of Menaquinone-7 Supplementation and Coronary Artery Calcification: A Randomized Clinical Trial. (2026). https://pubmed.ncbi.nlm.nih.gov/42268593/ DOI: 10.1001/jamacardio.2026.1279
Complete structured claim and evidence
UBIAD1-targeted siRNA inhibited labeled MK-4 formation in human cells.
Human UBIAD1 prenyltransferase → Menaquinone-4 biosynthesis source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/k2-research/20953171.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b8786e664d3b32db7b0cca72c710e24f1546e14f0a69c031908400731174cea3", "start_char": 0, "end_char": 2006, "text_sha256": "b8786e664d3b32db7b0cca72c710e24f1546e14f0a69c031908400731174cea3"}
experimental_model
Gene knockdown, heterologous expression, isotope conversion and NMR
exposure
Labeled vitamin K precursors, UBIAD1 knockdown and expression
limitations
Identifies a biosynthetic enzyme, not a clinical requirement to supplement MK-4. K1-derived MK-4 synthesis does not make humans independent of external vitamin K precursors.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Human UBIAD1 in human and insect-cell systems; mouse localization
plain_language
A synthesis defect is different from simply eating little K2.
primary_references
[k2-p20953171] Identification of UBIAD1 as a novel human menaquinone-4 biosynthetic enzyme. (2010). https://pubmed.ncbi.nlm.nih.gov/20953171/ DOI: 10.1038/nature09464
tissue_or_cell_type
MK-4 synthesis
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 149–160
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Gene knockdown, heterologous expression, isotope conversion and NMR · source_derived_draft · unverified_draft
### k2-ubiad1-knockdown UBIAD1-targeted siRNA inhibited labeled MK-4 formation in human cells. Condition category: machinery_impairment nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A synthesis defect is different from simply eating little K2. organism: Human UBIAD1 in human and insect-cell systems; mouse localization tissue_or_cell_type: MK-4 synthesis experimental_model: Gene knockdown, heterologous expression, isotope conversion and NMR limitations: Identifies a biosynthetic enzyme, not a clinical requirement to supplement MK-4. K1-derived MK-4 synthesis does not make humans independent of external vitamin K precursors. exposure: Labeled vitamin K precursors, UBIAD1 knockdown and expression evidence_span: {"source_cache": "artifacts/k2-research/20953171.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b8786e664d3b32db7b0cca72c710e24f1546e14f0a69c031908400731174cea3", "start_char": 0, "end_char": 2006, "text_sha256": "b8786e664d3b32db7b0cca72c710e24f1546e14f0a69c031908400731174cea3"} [k2-p20953171] Identification of UBIAD1 as a novel human menaquinone-4 biosynthetic enzyme. (2010). https://pubmed.ncbi.nlm.nih.gov/20953171/ DOI: 10.1038/nature09464
Complete structured claim and evidence
Warfarin did not inhibit UBIAD1-mediated MK-4 biosynthesis in the reported experiments.
Warfarin → Menaquinone-4 biosynthesis source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/20953171.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b8786e664d3b32db7b0cca72c710e24f1546e14f0a69c031908400731174cea3", "start_char": 0, "end_char": 2006, "text_sha256": "b8786e664d3b32db7b0cca72c710e24f1546e14f0a69c031908400731174cea3"}
experimental_model
Gene knockdown, heterologous expression, isotope conversion and NMR
exposure
Labeled vitamin K precursors, UBIAD1 knockdown and expression
limitations
Identifies a biosynthetic enzyme, not a clinical requirement to supplement MK-4. K1-derived MK-4 synthesis does not make humans independent of external vitamin K precursors.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Human UBIAD1 in human and insect-cell systems; mouse localization
plain_language
The drug blocks vitamin K recycling, but that is a different enzyme step from making MK-4.
primary_references
[k2-p20953171] Identification of UBIAD1 as a novel human menaquinone-4 biosynthetic enzyme. (2010). https://pubmed.ncbi.nlm.nih.gov/20953171/ DOI: 10.1038/nature09464
tissue_or_cell_type
MK-4 synthesis
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 162–173
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Gene knockdown, heterologous expression, isotope conversion and NMR · source_derived_draft · unverified_draft
### k2-ubiad1-warfarin Warfarin did not inhibit UBIAD1-mediated MK-4 biosynthesis in the reported experiments. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The drug blocks vitamin K recycling, but that is a different enzyme step from making MK-4. organism: Human UBIAD1 in human and insect-cell systems; mouse localization tissue_or_cell_type: MK-4 synthesis experimental_model: Gene knockdown, heterologous expression, isotope conversion and NMR limitations: Identifies a biosynthetic enzyme, not a clinical requirement to supplement MK-4. K1-derived MK-4 synthesis does not make humans independent of external vitamin K precursors. exposure: Labeled vitamin K precursors, UBIAD1 knockdown and expression evidence_span: {"source_cache": "artifacts/k2-research/20953171.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b8786e664d3b32db7b0cca72c710e24f1546e14f0a69c031908400731174cea3", "start_char": 0, "end_char": 2006, "text_sha256": "b8786e664d3b32db7b0cca72c710e24f1546e14f0a69c031908400731174cea3"} [k2-p20953171] Identification of UBIAD1 as a novel human menaquinone-4 biosynthetic enzyme. (2010). https://pubmed.ncbi.nlm.nih.gov/20953171/ DOI: 10.1038/nature09464
Complete structured claim and evidence
Rat tracer experiments identified menadione derived from oral phylloquinone as a circulating precursor of tissue MK-4.
Phylloquinone → Menadione / vitamin K3 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/24085302.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a0197882d517aa2bd4d9b2919e72c588383ad183064f1a2bf8f64f5152d28386", "start_char": 0, "end_char": 1653, "text_sha256": "a0197882d517aa2bd4d9b2919e72c588383ad183064f1a2bf8f64f5152d28386"}
experimental_model
Stable-isotope cannulation and recombinant-enzyme product analysis
exposure
Oral labeled phylloquinone; MS and NMR analysis
limitations
Rat tracing defines a precursor route; no exact human conversion fraction or advice to ingest menadione is inferred.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Rats and recombinant UBIAD1
plain_language
K1 and K2 metabolism connect through a precursor; they are not completely separate nutritional systems.
primary_references
[k2-p24085302] Menadione (vitamin K3) is a catabolic product of oral phylloquinone (vitamin K1) in the intestine and a circulating precursor of tissue menaquinone-4 (vitamin K2) in rats. (2013). https://pubmed.ncbi.nlm.nih.gov/24085302/ DOI: 10.1074/jbc.m113.477356
tissue_or_cell_type
Intestine, circulation and tissue synthesis
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 175–186
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Stable-isotope cannulation and recombinant-enzyme product analysis · source_derived_draft · unverified_draft
### k2-k1-menadione Rat tracer experiments identified menadione derived from oral phylloquinone as a circulating precursor of tissue MK-4. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: K1 and K2 metabolism connect through a precursor; they are not completely separate nutritional systems. organism: Rats and recombinant UBIAD1 tissue_or_cell_type: Intestine, circulation and tissue synthesis experimental_model: Stable-isotope cannulation and recombinant-enzyme product analysis limitations: Rat tracing defines a precursor route; no exact human conversion fraction or advice to ingest menadione is inferred. exposure: Oral labeled phylloquinone; MS and NMR analysis evidence_span: {"source_cache": "artifacts/k2-research/24085302.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a0197882d517aa2bd4d9b2919e72c588383ad183064f1a2bf8f64f5152d28386", "start_char": 0, "end_char": 1653, "text_sha256": "a0197882d517aa2bd4d9b2919e72c588383ad183064f1a2bf8f64f5152d28386"} [k2-p24085302] Menadione (vitamin K3) is a catabolic product of oral phylloquinone (vitamin K1) in the intestine and a circulating precursor of tissue menaquinone-4 (vitamin K2) in rats. (2013). https://pubmed.ncbi.nlm.nih.gov/24085302/ DOI: 10.1074/jbc.m113.477356
Complete structured claim and evidence
Product analysis identified reduced menadione, rather than its quinone form, as an intermediate in UBIAD1-mediated MK-4 formation.
Human UBIAD1 prenyltransferase → Menadiol / reduced menadione source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/24085302.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a0197882d517aa2bd4d9b2919e72c588383ad183064f1a2bf8f64f5152d28386", "start_char": 0, "end_char": 1653, "text_sha256": "a0197882d517aa2bd4d9b2919e72c588383ad183064f1a2bf8f64f5152d28386"}
experimental_model
Stable-isotope cannulation and recombinant-enzyme product analysis
exposure
Oral labeled phylloquinone; MS and NMR analysis
limitations
Rat tracing defines a precursor route; no exact human conversion fraction or advice to ingest menadione is inferred.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Rats and recombinant UBIAD1
plain_language
The precursor must also be in the right redox state.
primary_references
[k2-p24085302] Menadione (vitamin K3) is a catabolic product of oral phylloquinone (vitamin K1) in the intestine and a circulating precursor of tissue menaquinone-4 (vitamin K2) in rats. (2013). https://pubmed.ncbi.nlm.nih.gov/24085302/ DOI: 10.1074/jbc.m113.477356
tissue_or_cell_type
Intestine, circulation and tissue synthesis
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 188–199
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Stable-isotope cannulation and recombinant-enzyme product analysis · source_derived_draft · unverified_draft
### k2-reduced-precursor Product analysis identified reduced menadione, rather than its quinone form, as an intermediate in UBIAD1-mediated MK-4 formation. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The precursor must also be in the right redox state. organism: Rats and recombinant UBIAD1 tissue_or_cell_type: Intestine, circulation and tissue synthesis experimental_model: Stable-isotope cannulation and recombinant-enzyme product analysis limitations: Rat tracing defines a precursor route; no exact human conversion fraction or advice to ingest menadione is inferred. exposure: Oral labeled phylloquinone; MS and NMR analysis evidence_span: {"source_cache": "artifacts/k2-research/24085302.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a0197882d517aa2bd4d9b2919e72c588383ad183064f1a2bf8f64f5152d28386", "start_char": 0, "end_char": 1653, "text_sha256": "a0197882d517aa2bd4d9b2919e72c588383ad183064f1a2bf8f64f5152d28386"} [k2-p24085302] Menadione (vitamin K3) is a catabolic product of oral phylloquinone (vitamin K1) in the intestine and a circulating precursor of tissue menaquinone-4 (vitamin K2) in rats. (2013). https://pubmed.ncbi.nlm.nih.gov/24085302/ DOI: 10.1074/jbc.m113.477356
Complete structured claim and evidence
UBIAD1 synthesized MK-4 using GGPP as the isoprenyl side-chain source.
Human UBIAD1 prenyltransferase → Geranylgeranyl diphosphate / GGPP source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/25874989.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bbd73607ba2570aa383c81c189b29dd19f1cbd7bf7acdd8343ecf3ee7dc5faf8", "start_char": 24159, "end_char": 24399, "text_sha256": "b680e2031495b2fee24a56c799e8cb2f64bbac3c6a3cb0d33592051f2cf41b9f"}
experimental_model
Microsomal enzyme assays and mutagenesis
exposure
Prenyl donors, reductant, magnesium and lipophilic statins
limitations
In-vitro substrate and assay context. Residual microsomal magnesium prevents concluding that synthesis is magnesium-independent; no human supplementation effect was tested.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Human UBIAD1 expressed in Sf9 insect cells
plain_language
MK-4 production needs a side-chain donor as well as the vitamin K ring.
primary_references
[k2-p25874989] Functional characterization of the vitamin K2 biosynthetic enzyme UBIAD1. (2015). https://pubmed.ncbi.nlm.nih.gov/25874989/ DOI: 10.1371/journal.pone.0125737
tissue_or_cell_type
Microsomal prenylation
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 201–212
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Microsomal enzyme assays and mutagenesis · source_derived_draft · unverified_draft
### k2-ggpp-sidechain UBIAD1 synthesized MK-4 using GGPP as the isoprenyl side-chain source. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: MK-4 production needs a side-chain donor as well as the vitamin K ring. organism: Human UBIAD1 expressed in Sf9 insect cells tissue_or_cell_type: Microsomal prenylation experimental_model: Microsomal enzyme assays and mutagenesis limitations: In-vitro substrate and assay context. Residual microsomal magnesium prevents concluding that synthesis is magnesium-independent; no human supplementation effect was tested. exposure: Prenyl donors, reductant, magnesium and lipophilic statins evidence_span: {"source_cache": "artifacts/k2-research/25874989.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bbd73607ba2570aa383c81c189b29dd19f1cbd7bf7acdd8343ecf3ee7dc5faf8", "start_char": 24159, "end_char": 24399, "text_sha256": "b680e2031495b2fee24a56c799e8cb2f64bbac3c6a3cb0d33592051f2cf41b9f"} [k2-p25874989] Functional characterization of the vitamin K2 biosynthetic enzyme UBIAD1. (2015). https://pubmed.ncbi.nlm.nih.gov/25874989/ DOI: 10.1371/journal.pone.0125737
Complete structured claim and evidence
Mutational analysis assigned conserved domain IV to magnesium/isoprenyl-side-chain interactions.
Human UBIAD1 prenyltransferase → Mg2+ source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/25874989.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a3eb5f4c56ca7a3e70a32c020bba09f4fec5e91048b13a188017bf221f713a68", "start_char": 0, "end_char": 1777, "text_sha256": "a3eb5f4c56ca7a3e70a32c020bba09f4fec5e91048b13a188017bf221f713a68"}
experimental_model
Microsomal enzyme assays and mutagenesis
exposure
Prenyl donors, reductant, magnesium and lipophilic statins
limitations
In-vitro substrate and assay context. Residual microsomal magnesium prevents concluding that synthesis is magnesium-independent; no human supplementation effect was tested.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Human UBIAD1 expressed in Sf9 insect cells
plain_language
Magnesium-related enzyme chemistry is recorded separately from a claim that oral magnesium improves K2 status.
primary_references
[k2-p25874989] Functional characterization of the vitamin K2 biosynthetic enzyme UBIAD1. (2015). https://pubmed.ncbi.nlm.nih.gov/25874989/ DOI: 10.1371/journal.pone.0125737
tissue_or_cell_type
Microsomal prenylation
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 214–225
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Microsomal enzyme assays and mutagenesis · source_derived_draft · unverified_draft
### k2-ubiad1-magnesium-site Mutational analysis assigned conserved domain IV to magnesium/isoprenyl-side-chain interactions. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium-related enzyme chemistry is recorded separately from a claim that oral magnesium improves K2 status. organism: Human UBIAD1 expressed in Sf9 insect cells tissue_or_cell_type: Microsomal prenylation experimental_model: Microsomal enzyme assays and mutagenesis limitations: In-vitro substrate and assay context. Residual microsomal magnesium prevents concluding that synthesis is magnesium-independent; no human supplementation effect was tested. exposure: Prenyl donors, reductant, magnesium and lipophilic statins evidence_span: {"source_cache": "artifacts/k2-research/25874989.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a3eb5f4c56ca7a3e70a32c020bba09f4fec5e91048b13a188017bf221f713a68", "start_char": 0, "end_char": 1777, "text_sha256": "a3eb5f4c56ca7a3e70a32c020bba09f4fec5e91048b13a188017bf221f713a68"} [k2-p25874989] Functional characterization of the vitamin K2 biosynthetic enzyme UBIAD1. (2015). https://pubmed.ncbi.nlm.nih.gov/25874989/ DOI: 10.1371/journal.pone.0125737
Complete structured claim and evidence
High added magnesium inhibited MK-4 synthesis with GGPP in the microsomal assay; residual microsomal magnesium prevented a zero-magnesium conclusion.
Mg2+ → Menaquinone-4 biosynthesis source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/25874989.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bbd73607ba2570aa383c81c189b29dd19f1cbd7bf7acdd8343ecf3ee7dc5faf8", "start_char": 45325, "end_char": 45633, "text_sha256": "6ae5b000cbc7fa6b682d2b2a915102061ea7bd2e3a3941a1bce8ed98ce0ee016"}
experimental_model
Microsomal enzyme assays and mutagenesis
exposure
Prenyl donors, reductant, magnesium and lipophilic statins
limitations
In-vitro substrate and assay context. Residual microsomal magnesium prevents concluding that synthesis is magnesium-independent; no human supplementation effect was tested.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Human UBIAD1 expressed in Sf9 insect cells
plain_language
More of a cofactor is not automatically better in an enzyme assay.
primary_references
[k2-p25874989] Functional characterization of the vitamin K2 biosynthetic enzyme UBIAD1. (2015). https://pubmed.ncbi.nlm.nih.gov/25874989/ DOI: 10.1371/journal.pone.0125737
tissue_or_cell_type
Microsomal prenylation
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 227–238
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Microsomal enzyme assays and mutagenesis · source_derived_draft · unverified_draft
### k2-magnesium-context High added magnesium inhibited MK-4 synthesis with GGPP in the microsomal assay; residual microsomal magnesium prevented a zero-magnesium conclusion. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: More of a cofactor is not automatically better in an enzyme assay. organism: Human UBIAD1 expressed in Sf9 insect cells tissue_or_cell_type: Microsomal prenylation experimental_model: Microsomal enzyme assays and mutagenesis limitations: In-vitro substrate and assay context. Residual microsomal magnesium prevents concluding that synthesis is magnesium-independent; no human supplementation effect was tested. exposure: Prenyl donors, reductant, magnesium and lipophilic statins evidence_span: {"source_cache": "artifacts/k2-research/25874989.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bbd73607ba2570aa383c81c189b29dd19f1cbd7bf7acdd8343ecf3ee7dc5faf8", "start_char": 45325, "end_char": 45633, "text_sha256": "6ae5b000cbc7fa6b682d2b2a915102061ea7bd2e3a3941a1bce8ed98ce0ee016"} [k2-p25874989] Functional characterization of the vitamin K2 biosynthetic enzyme UBIAD1. (2015). https://pubmed.ncbi.nlm.nih.gov/25874989/ DOI: 10.1371/journal.pone.0125737
Complete structured claim and evidence
UBIAD1 N102S retained about 82% of MK-4 biosynthetic activity and did not impair reporter carboxylation.
Human UBIAD1 prenyltransferase → Vitamin K-dependent protein gamma-carboxylation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/k2-research/34813684.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f533947abd5f26101d1bf1e2548d37b98d16bb72c470dcdfaf2b2f2625c5e206", "start_char": 0, "end_char": 1777, "text_sha256": "f533947abd5f26101d1bf1e2548d37b98d16bb72c470dcdfaf2b2f2625c5e206"}
experimental_model
CRISPR reporter cells with UBIAD1 variants
exposure
UBIAD1 N102S, G186R and other variants
limitations
Cell-specific residual activity differs between variants; a UBIAD1 mutation is not automatically global vitamin K failure.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Human HEK293 reporter cells
plain_language
A partial synthesis change did not automatically disable the downstream reaction.
primary_references
[k2-p34813684] Naturally occurring UBIAD1 mutations differentially affect menaquinone biosynthesis and vitamin K-dependent carboxylation. (2022). https://pubmed.ncbi.nlm.nih.gov/34813684/ DOI: 10.1111/febs.16291
tissue_or_cell_type
MK-4 production and protein carboxylation
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 240–251
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · CRISPR reporter cells with UBIAD1 variants · source_derived_draft · unverified_draft
### k2-ubiad1-n102s UBIAD1 N102S retained about 82% of MK-4 biosynthetic activity and did not impair reporter carboxylation. Condition category: machinery_impairment nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A partial synthesis change did not automatically disable the downstream reaction. organism: Human HEK293 reporter cells tissue_or_cell_type: MK-4 production and protein carboxylation experimental_model: CRISPR reporter cells with UBIAD1 variants limitations: Cell-specific residual activity differs between variants; a UBIAD1 mutation is not automatically global vitamin K failure. exposure: UBIAD1 N102S, G186R and other variants evidence_span: {"source_cache": "artifacts/k2-research/34813684.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f533947abd5f26101d1bf1e2548d37b98d16bb72c470dcdfaf2b2f2625c5e206", "start_char": 0, "end_char": 1777, "text_sha256": "f533947abd5f26101d1bf1e2548d37b98d16bb72c470dcdfaf2b2f2625c5e206"} [k2-p34813684] Naturally occurring UBIAD1 mutations differentially affect menaquinone biosynthesis and vitamin K-dependent carboxylation. (2022). https://pubmed.ncbi.nlm.nih.gov/34813684/ DOI: 10.1111/febs.16291
Complete structured claim and evidence
UBIAD1 G186R significantly impaired both MK-4 biosynthesis and vitamin K-dependent reporter carboxylation.
Human UBIAD1 prenyltransferase → Vitamin K-dependent protein gamma-carboxylation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/k2-research/34813684.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f533947abd5f26101d1bf1e2548d37b98d16bb72c470dcdfaf2b2f2625c5e206", "start_char": 0, "end_char": 1777, "text_sha256": "f533947abd5f26101d1bf1e2548d37b98d16bb72c470dcdfaf2b2f2625c5e206"}
experimental_model
CRISPR reporter cells with UBIAD1 variants
exposure
UBIAD1 N102S, G186R and other variants
limitations
Cell-specific residual activity differs between variants; a UBIAD1 mutation is not automatically global vitamin K failure.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Human HEK293 reporter cells
plain_language
A different variant impaired both supply and use in the same assay.
primary_references
[k2-p34813684] Naturally occurring UBIAD1 mutations differentially affect menaquinone biosynthesis and vitamin K-dependent carboxylation. (2022). https://pubmed.ncbi.nlm.nih.gov/34813684/ DOI: 10.1111/febs.16291
tissue_or_cell_type
MK-4 production and protein carboxylation
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 253–264
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · CRISPR reporter cells with UBIAD1 variants · source_derived_draft · unverified_draft
### k2-ubiad1-g186r UBIAD1 G186R significantly impaired both MK-4 biosynthesis and vitamin K-dependent reporter carboxylation. Condition category: machinery_impairment nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A different variant impaired both supply and use in the same assay. organism: Human HEK293 reporter cells tissue_or_cell_type: MK-4 production and protein carboxylation experimental_model: CRISPR reporter cells with UBIAD1 variants limitations: Cell-specific residual activity differs between variants; a UBIAD1 mutation is not automatically global vitamin K failure. exposure: UBIAD1 N102S, G186R and other variants evidence_span: {"source_cache": "artifacts/k2-research/34813684.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f533947abd5f26101d1bf1e2548d37b98d16bb72c470dcdfaf2b2f2625c5e206", "start_char": 0, "end_char": 1777, "text_sha256": "f533947abd5f26101d1bf1e2548d37b98d16bb72c470dcdfaf2b2f2625c5e206"} [k2-p34813684] Naturally occurring UBIAD1 mutations differentially affect menaquinone biosynthesis and vitamin K-dependent carboxylation. (2022). https://pubmed.ncbi.nlm.nih.gov/34813684/ DOI: 10.1111/febs.16291
Complete structured claim and evidence
Serum MK-7 peaked six hours after the single dose, remained detectable to 48 hours, and rose during seven-day dosing.
Menaquinone-7 / MK-7 → Serum menaquinone-7 concentration source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/23140417.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e72bb9c0cc5800cba0605d7abba2c4e6c113dda5fa0e9b4a3afff898b23a97c4", "start_char": 0, "end_char": 1328, "text_sha256": "e72bb9c0cc5800cba0605d7abba2c4e6c113dda5fa0e9b4a3afff898b23a97c4"}
experimental_model
Single-dose and seven-day nutritional-dose comparison
exposure
420 micrograms single dose or 60 micrograms/day for seven days; MK-4 versus MK-7
limitations
Small parallel groups; equal mass is not equal molar dose. Undetectable serum MK-4 does not prove absent absorption, absent tissue delivery or clinical ineffectiveness.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Healthy young Japanese women
plain_language
This K2 form remained measurable in blood across a longer sampling window.
primary_references
[k2-p23140417] Comparison of menaquinone-4 and menaquinone-7 bioavailability in healthy women. (2012). https://pubmed.ncbi.nlm.nih.gov/23140417/ DOI: 10.1186/1475-2891-11-93
tissue_or_cell_type
Serum vitamin K concentrations
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 266–277
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Single-dose and seven-day nutritional-dose comparison · source_derived_draft · unverified_draft
### k2-mk7-serum Serum MK-7 peaked six hours after the single dose, remained detectable to 48 hours, and rose during seven-day dosing. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: This K2 form remained measurable in blood across a longer sampling window. organism: Healthy young Japanese women tissue_or_cell_type: Serum vitamin K concentrations experimental_model: Single-dose and seven-day nutritional-dose comparison limitations: Small parallel groups; equal mass is not equal molar dose. Undetectable serum MK-4 does not prove absent absorption, absent tissue delivery or clinical ineffectiveness. exposure: 420 micrograms single dose or 60 micrograms/day for seven days; MK-4 versus MK-7 evidence_span: {"source_cache": "artifacts/k2-research/23140417.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e72bb9c0cc5800cba0605d7abba2c4e6c113dda5fa0e9b4a3afff898b23a97c4", "start_char": 0, "end_char": 1328, "text_sha256": "e72bb9c0cc5800cba0605d7abba2c4e6c113dda5fa0e9b4a3afff898b23a97c4"} [k2-p23140417] Comparison of menaquinone-4 and menaquinone-7 bioavailability in healthy women. (2012). https://pubmed.ncbi.nlm.nih.gov/23140417/ DOI: 10.1186/1475-2891-11-93
Complete structured claim and evidence
MK-4 was not detected in serum after the tested 420-microgram dose and serum MK-4 did not increase with the seven-day 60-microgram regimen.
Menaquinone-4 / MK-4 / menatetrenone → Serum menaquinone-4 concentration source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/23140417.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e72bb9c0cc5800cba0605d7abba2c4e6c113dda5fa0e9b4a3afff898b23a97c4", "start_char": 0, "end_char": 1328, "text_sha256": "e72bb9c0cc5800cba0605d7abba2c4e6c113dda5fa0e9b4a3afff898b23a97c4"}
experimental_model
Single-dose and seven-day nutritional-dose comparison
exposure
420 micrograms single dose or 60 micrograms/day for seven days; MK-4 versus MK-7
limitations
Small parallel groups; equal mass is not equal molar dose. Undetectable serum MK-4 does not prove absent absorption, absent tissue delivery or clinical ineffectiveness.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Healthy young Japanese women
plain_language
The blood test behaved differently for MK-4; that does not tell us that none reached tissues.
primary_references
[k2-p23140417] Comparison of menaquinone-4 and menaquinone-7 bioavailability in healthy women. (2012). https://pubmed.ncbi.nlm.nih.gov/23140417/ DOI: 10.1186/1475-2891-11-93
tissue_or_cell_type
Serum vitamin K concentrations
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 279–290
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Single-dose and seven-day nutritional-dose comparison · source_derived_draft · unverified_draft
### k2-mk4-serum MK-4 was not detected in serum after the tested 420-microgram dose and serum MK-4 did not increase with the seven-day 60-microgram regimen. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The blood test behaved differently for MK-4; that does not tell us that none reached tissues. organism: Healthy young Japanese women tissue_or_cell_type: Serum vitamin K concentrations experimental_model: Single-dose and seven-day nutritional-dose comparison limitations: Small parallel groups; equal mass is not equal molar dose. Undetectable serum MK-4 does not prove absent absorption, absent tissue delivery or clinical ineffectiveness. exposure: 420 micrograms single dose or 60 micrograms/day for seven days; MK-4 versus MK-7 evidence_span: {"source_cache": "artifacts/k2-research/23140417.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e72bb9c0cc5800cba0605d7abba2c4e6c113dda5fa0e9b4a3afff898b23a97c4", "start_char": 0, "end_char": 1328, "text_sha256": "e72bb9c0cc5800cba0605d7abba2c4e6c113dda5fa0e9b4a3afff898b23a97c4"} [k2-p23140417] Comparison of menaquinone-4 and menaquinone-7 bioavailability in healthy women. (2012). https://pubmed.ncbi.nlm.nih.gov/23140417/ DOI: 10.1186/1475-2891-11-93
Complete structured claim and evidence
MK-7 produced more complete osteocalcin carboxylation than the compared K1 regimen.
Menaquinone-7 / MK-7 → Gamma-carboxylated osteocalcin source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/17158229.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1bf2196600220143fbc5ba85e8aba71b4c8aa931f4a6c47545c3db9570283faf", "start_char": 0, "end_char": 1248, "text_sha256": "1bf2196600220143fbc5ba85e8aba71b4c8aa931f4a6c47545c3db9570283faf"}
experimental_model
Comparative human absorption and activity experiments
exposure
Phylloquinone versus natto-derived MK-7
limitations
Biochemical exposure and activity endpoints, not fracture or cardiovascular-event prevention.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Healthy volunteers
plain_language
The biochemical modification changed; clinical bone outcomes were a separate question.
primary_references
[k2-p17158229] Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7. (2007). https://pubmed.ncbi.nlm.nih.gov/17158229/ DOI: 10.1182/blood-2006-08-040709
tissue_or_cell_type
Serum vitamers and osteocalcin
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 305–316
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Comparative human absorption and activity experiments · source_derived_draft · unverified_draft
### k2-mk7-oc-carboxylation MK-7 produced more complete osteocalcin carboxylation than the compared K1 regimen. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The biochemical modification changed; clinical bone outcomes were a separate question. organism: Healthy volunteers tissue_or_cell_type: Serum vitamers and osteocalcin experimental_model: Comparative human absorption and activity experiments limitations: Biochemical exposure and activity endpoints, not fracture or cardiovascular-event prevention. exposure: Phylloquinone versus natto-derived MK-7 evidence_span: {"source_cache": "artifacts/k2-research/17158229.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1bf2196600220143fbc5ba85e8aba71b4c8aa931f4a6c47545c3db9570283faf", "start_char": 0, "end_char": 1248, "text_sha256": "1bf2196600220143fbc5ba85e8aba71b4c8aa931f4a6c47545c3db9570283faf"} [k2-p17158229] Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7. (2007). https://pubmed.ncbi.nlm.nih.gov/17158229/ DOI: 10.1182/blood-2006-08-040709
Complete structured claim and evidence
Purified CYP4F2 catalyzed MK-4 terminal side-chain hydroxylation in vitro.
Human cytochrome P450 4F2 → Menaquinone-4 / MK-4 / menatetrenone source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/24138531.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bcb3784026ddabfeb55257cddc84ffd1001d6eb4fb04ba2e9daf8ade8de770fb", "start_char": 0, "end_char": 1608, "text_sha256": "bcb3784026ddabfeb55257cddc84ffd1001d6eb4fb04ba2e9daf8ade8de770fb"}
experimental_model
Purified enzymes, liver microsomes and genotyping
exposure
MK-4 oxidation and common enzyme variants
limitations
Catabolism assay; no assumption that all long-chain menaquinones have identical kinetics.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Human CYP4F2/CYP4F11 and human liver microsomes
plain_language
An enzyme begins breaking down MK-4 by modifying the end of its side chain.
primary_references
[k2-p24138531] Cytochrome P450-dependent catabolism of vitamin K: ω-hydroxylation catalyzed by human CYP4F2 and CYP4F11. (2013). https://pubmed.ncbi.nlm.nih.gov/24138531/ DOI: 10.1021/bi401208m
tissue_or_cell_type
MK-4 catabolism
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 318–329
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified enzymes, liver microsomes and genotyping · source_derived_draft · unverified_draft
### k2-cyp4f2-mk4 Purified CYP4F2 catalyzed MK-4 terminal side-chain hydroxylation in vitro. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: An enzyme begins breaking down MK-4 by modifying the end of its side chain. organism: Human CYP4F2/CYP4F11 and human liver microsomes tissue_or_cell_type: MK-4 catabolism experimental_model: Purified enzymes, liver microsomes and genotyping limitations: Catabolism assay; no assumption that all long-chain menaquinones have identical kinetics. exposure: MK-4 oxidation and common enzyme variants evidence_span: {"source_cache": "artifacts/k2-research/24138531.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bcb3784026ddabfeb55257cddc84ffd1001d6eb4fb04ba2e9daf8ade8de770fb", "start_char": 0, "end_char": 1608, "text_sha256": "bcb3784026ddabfeb55257cddc84ffd1001d6eb4fb04ba2e9daf8ade8de770fb"} [k2-p24138531] Cytochrome P450-dependent catabolism of vitamin K: ω-hydroxylation catalyzed by human CYP4F2 and CYP4F11. (2013). https://pubmed.ncbi.nlm.nih.gov/24138531/ DOI: 10.1021/bi401208m
Complete structured claim and evidence
Purified CYP4F11 catalyzed MK-4 terminal side-chain hydroxylation in vitro.
Human cytochrome P450 4F11 → Menaquinone-4 / MK-4 / menatetrenone source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/24138531.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bcb3784026ddabfeb55257cddc84ffd1001d6eb4fb04ba2e9daf8ade8de770fb", "start_char": 0, "end_char": 1608, "text_sha256": "bcb3784026ddabfeb55257cddc84ffd1001d6eb4fb04ba2e9daf8ade8de770fb"}
experimental_model
Purified enzymes, liver microsomes and genotyping
exposure
MK-4 oxidation and common enzyme variants
limitations
Catabolism assay; no assumption that all long-chain menaquinones have identical kinetics.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Human CYP4F2/CYP4F11 and human liver microsomes
plain_language
An enzyme begins breaking down MK-4 by modifying the end of its side chain.
primary_references
[k2-p24138531] Cytochrome P450-dependent catabolism of vitamin K: ω-hydroxylation catalyzed by human CYP4F2 and CYP4F11. (2013). https://pubmed.ncbi.nlm.nih.gov/24138531/ DOI: 10.1021/bi401208m
tissue_or_cell_type
MK-4 catabolism
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 331–342
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified enzymes, liver microsomes and genotyping · source_derived_draft · unverified_draft
### k2-cyp4f11-mk4 Purified CYP4F11 catalyzed MK-4 terminal side-chain hydroxylation in vitro. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: An enzyme begins breaking down MK-4 by modifying the end of its side chain. organism: Human CYP4F2/CYP4F11 and human liver microsomes tissue_or_cell_type: MK-4 catabolism experimental_model: Purified enzymes, liver microsomes and genotyping limitations: Catabolism assay; no assumption that all long-chain menaquinones have identical kinetics. exposure: MK-4 oxidation and common enzyme variants evidence_span: {"source_cache": "artifacts/k2-research/24138531.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bcb3784026ddabfeb55257cddc84ffd1001d6eb4fb04ba2e9daf8ade8de770fb", "start_char": 0, "end_char": 1608, "text_sha256": "bcb3784026ddabfeb55257cddc84ffd1001d6eb4fb04ba2e9daf8ade8de770fb"} [k2-p24138531] Cytochrome P450-dependent catabolism of vitamin K: ω-hydroxylation catalyzed by human CYP4F2 and CYP4F11. (2013). https://pubmed.ncbi.nlm.nih.gov/24138531/ DOI: 10.1021/bi401208m
Complete structured claim and evidence
CYP4F2, but not CYP4F11, supported sequential MK-4 oxidation to the omega-acid without apparent release of the aldehyde intermediate.
Human cytochrome P450 4F2 → Menaquinone-4 omega-carboxylic acid source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/24138531.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bcb3784026ddabfeb55257cddc84ffd1001d6eb4fb04ba2e9daf8ade8de770fb", "start_char": 0, "end_char": 1608, "text_sha256": "bcb3784026ddabfeb55257cddc84ffd1001d6eb4fb04ba2e9daf8ade8de770fb"}
experimental_model
Purified enzymes, liver microsomes and genotyping
exposure
MK-4 oxidation and common enzyme variants
limitations
Catabolism assay; no assumption that all long-chain menaquinones have identical kinetics.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Human CYP4F2/CYP4F11 and human liver microsomes
plain_language
The two enzymes did not perform every later breakdown step equally.
primary_references
[k2-p24138531] Cytochrome P450-dependent catabolism of vitamin K: ω-hydroxylation catalyzed by human CYP4F2 and CYP4F11. (2013). https://pubmed.ncbi.nlm.nih.gov/24138531/ DOI: 10.1021/bi401208m
tissue_or_cell_type
MK-4 catabolism
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 344–355
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified enzymes, liver microsomes and genotyping · source_derived_draft · unverified_draft
### k2-cyp4f2-acid CYP4F2, but not CYP4F11, supported sequential MK-4 oxidation to the omega-acid without apparent release of the aldehyde intermediate. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The two enzymes did not perform every later breakdown step equally. organism: Human CYP4F2/CYP4F11 and human liver microsomes tissue_or_cell_type: MK-4 catabolism experimental_model: Purified enzymes, liver microsomes and genotyping limitations: Catabolism assay; no assumption that all long-chain menaquinones have identical kinetics. exposure: MK-4 oxidation and common enzyme variants evidence_span: {"source_cache": "artifacts/k2-research/24138531.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bcb3784026ddabfeb55257cddc84ffd1001d6eb4fb04ba2e9daf8ade8de770fb", "start_char": 0, "end_char": 1608, "text_sha256": "bcb3784026ddabfeb55257cddc84ffd1001d6eb4fb04ba2e9daf8ade8de770fb"} [k2-p24138531] Cytochrome P450-dependent catabolism of vitamin K: ω-hydroxylation catalyzed by human CYP4F2 and CYP4F11. (2013). https://pubmed.ncbi.nlm.nih.gov/24138531/ DOI: 10.1021/bi401208m
Complete structured claim and evidence
Microsomal NAD-dependent alcohol and aldehyde dehydrogenase activities converted the MK-4 omega-alcohol to its acid.
NAD+ → Omega-hydroxymenaquinone-4 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/24138531.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bcb3784026ddabfeb55257cddc84ffd1001d6eb4fb04ba2e9daf8ade8de770fb", "start_char": 0, "end_char": 1608, "text_sha256": "bcb3784026ddabfeb55257cddc84ffd1001d6eb4fb04ba2e9daf8ade8de770fb"}
experimental_model
Purified enzymes, liver microsomes and genotyping
exposure
MK-4 oxidation and common enzyme variants
limitations
Catabolism assay; no assumption that all long-chain menaquinones have identical kinetics.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Human CYP4F2/CYP4F11 and human liver microsomes
plain_language
Niacin-derived NAD participates in an alternative route through the breakdown sequence.
primary_references
[k2-p24138531] Cytochrome P450-dependent catabolism of vitamin K: ω-hydroxylation catalyzed by human CYP4F2 and CYP4F11. (2013). https://pubmed.ncbi.nlm.nih.gov/24138531/ DOI: 10.1021/bi401208m
tissue_or_cell_type
MK-4 catabolism
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 357–368
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified enzymes, liver microsomes and genotyping · source_derived_draft · unverified_draft
### k2-mk4-nad-catabolism Microsomal NAD-dependent alcohol and aldehyde dehydrogenase activities converted the MK-4 omega-alcohol to its acid. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Niacin-derived NAD participates in an alternative route through the breakdown sequence. organism: Human CYP4F2/CYP4F11 and human liver microsomes tissue_or_cell_type: MK-4 catabolism experimental_model: Purified enzymes, liver microsomes and genotyping limitations: Catabolism assay; no assumption that all long-chain menaquinones have identical kinetics. exposure: MK-4 oxidation and common enzyme variants evidence_span: {"source_cache": "artifacts/k2-research/24138531.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bcb3784026ddabfeb55257cddc84ffd1001d6eb4fb04ba2e9daf8ade8de770fb", "start_char": 0, "end_char": 1608, "text_sha256": "bcb3784026ddabfeb55257cddc84ffd1001d6eb4fb04ba2e9daf8ade8de770fb"} [k2-p24138531] Cytochrome P450-dependent catabolism of vitamin K: ω-hydroxylation catalyzed by human CYP4F2 and CYP4F11. (2013). https://pubmed.ncbi.nlm.nih.gov/24138531/ DOI: 10.1021/bi401208m
Complete structured claim and evidence
Vitamin K-dependent protein propeptide binding stabilized GGCX transmembrane helices 6 and 7 and created its vitamin-K-binding pocket.
Osteocalcin / BGLAP → Gamma-glutamyl carboxylase / GGCX source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/39880952.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "eb8e6d00eecd7c5c780921cae3f804fab60e919301eeb16e9909f36293aaa653", "start_char": 0, "end_char": 1230, "text_sha256": "eb8e6d00eecd7c5c780921cae3f804fab60e919301eeb16e9909f36293aaa653"}
experimental_model
Cryo-EM, binding, cell assays and molecular dynamics
exposure
Apo, osteocalcin-bound and vitamin-K-bound structures
limitations
Shared vitamin K chemistry; the abstract does not establish K2 exclusivity or identical kinetics for every menaquinone.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Human GGCX
plain_language
The target protein helps organize the enzyme that modifies it.
primary_references
[k2-p39880952] Structure and mechanism of vitamin-K-dependent γ-glutamyl carboxylase. (2025). https://pubmed.ncbi.nlm.nih.gov/39880952/ DOI: 10.1038/s41586-024-08484-9
tissue_or_cell_type
Endoplasmic-reticulum membrane enzyme
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 383–394
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cryo-EM, binding, cell assays and molecular dynamics · source_derived_draft · unverified_draft
### k2-ggcx-osteocalcin-binding Vitamin K-dependent protein propeptide binding stabilized GGCX transmembrane helices 6 and 7 and created its vitamin-K-binding pocket. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The target protein helps organize the enzyme that modifies it. organism: Human GGCX tissue_or_cell_type: Endoplasmic-reticulum membrane enzyme experimental_model: Cryo-EM, binding, cell assays and molecular dynamics limitations: Shared vitamin K chemistry; the abstract does not establish K2 exclusivity or identical kinetics for every menaquinone. exposure: Apo, osteocalcin-bound and vitamin-K-bound structures evidence_span: {"source_cache": "artifacts/k2-research/39880952.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "eb8e6d00eecd7c5c780921cae3f804fab60e919301eeb16e9909f36293aaa653", "start_char": 0, "end_char": 1230, "text_sha256": "eb8e6d00eecd7c5c780921cae3f804fab60e919301eeb16e9909f36293aaa653"} [k2-p39880952] Structure and mechanism of vitamin-K-dependent γ-glutamyl carboxylase. (2025). https://pubmed.ncbi.nlm.nih.gov/39880952/ DOI: 10.1038/s41586-024-08484-9
Complete structured claim and evidence
A cholesterol molecule interacted with GGCX transmembrane helices; structural, cellular and simulation results connected this site with regulation of cellular GGCX protein levels.
Cholesterol → Gamma-glutamyl carboxylase / GGCX source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/39880952.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "eb8e6d00eecd7c5c780921cae3f804fab60e919301eeb16e9909f36293aaa653", "start_char": 0, "end_char": 1230, "text_sha256": "eb8e6d00eecd7c5c780921cae3f804fab60e919301eeb16e9909f36293aaa653"}
experimental_model
Cryo-EM, binding, cell assays and molecular dynamics
exposure
Apo, osteocalcin-bound and vitamin-K-bound structures
limitations
Shared vitamin K chemistry; the abstract does not establish K2 exclusivity or identical kinetics for every menaquinone.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Human GGCX
plain_language
Membrane cholesterol is part of the enzyme environment, not just an unrelated blood measurement.
primary_references
[k2-p39880952] Structure and mechanism of vitamin-K-dependent γ-glutamyl carboxylase. (2025). https://pubmed.ncbi.nlm.nih.gov/39880952/ DOI: 10.1038/s41586-024-08484-9
tissue_or_cell_type
Endoplasmic-reticulum membrane enzyme
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 396–407
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cryo-EM, binding, cell assays and molecular dynamics · source_derived_draft · unverified_draft
### k2-ggcx-cholesterol A cholesterol molecule interacted with GGCX transmembrane helices; structural, cellular and simulation results connected this site with regulation of cellular GGCX protein levels. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Membrane cholesterol is part of the enzyme environment, not just an unrelated blood measurement. organism: Human GGCX tissue_or_cell_type: Endoplasmic-reticulum membrane enzyme experimental_model: Cryo-EM, binding, cell assays and molecular dynamics limitations: Shared vitamin K chemistry; the abstract does not establish K2 exclusivity or identical kinetics for every menaquinone. exposure: Apo, osteocalcin-bound and vitamin-K-bound structures evidence_span: {"source_cache": "artifacts/k2-research/39880952.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "eb8e6d00eecd7c5c780921cae3f804fab60e919301eeb16e9909f36293aaa653", "start_char": 0, "end_char": 1230, "text_sha256": "eb8e6d00eecd7c5c780921cae3f804fab60e919301eeb16e9909f36293aaa653"} [k2-p39880952] Structure and mechanism of vitamin-K-dependent γ-glutamyl carboxylase. (2025). https://pubmed.ncbi.nlm.nih.gov/39880952/ DOI: 10.1038/s41586-024-08484-9
Complete structured claim and evidence
A conserved dipeptide-anchoring mechanism supports repeated glutamate carboxylation while a substrate remains associated with GGCX.
Gamma-glutamyl carboxylase / GGCX → Vitamin K-dependent protein gamma-carboxylation source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/41290650.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0ea90e4c1af519fa0fc3645f4a4f8f0721924797e0eaa44569ff445c4afe19bc", "start_char": 0, "end_char": 1177, "text_sha256": "0ea90e4c1af519fa0fc3645f4a4f8f0721924797e0eaa44569ff445c4afe19bc"}
experimental_model
Cryo-EM, mutagenesis and molecular dynamics
exposure
GGCX complexes with vitamin K, clotting-factor substrates and osteocalcin
limitations
Structural and biochemical model; the proposed bicarbonate proton relay is not a demonstrated benefit of bicarbonate ingestion.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Human GGCX
plain_language
The enzyme can modify several sites on the same protein during one encounter.
primary_references
[k2-p41290650] Structural insight into bicarbonate-mediated carboxylation by human vitamin K-dependent carboxylase. (2025). https://pubmed.ncbi.nlm.nih.gov/41290650/ DOI: 10.1038/s41467-025-65488-3
tissue_or_cell_type
Substrate recognition and carbon-dioxide capture
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 409–420
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cryo-EM, mutagenesis and molecular dynamics · source_derived_draft · unverified_draft
### k2-ggcx-processivity A conserved dipeptide-anchoring mechanism supports repeated glutamate carboxylation while a substrate remains associated with GGCX. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The enzyme can modify several sites on the same protein during one encounter. organism: Human GGCX tissue_or_cell_type: Substrate recognition and carbon-dioxide capture experimental_model: Cryo-EM, mutagenesis and molecular dynamics limitations: Structural and biochemical model; the proposed bicarbonate proton relay is not a demonstrated benefit of bicarbonate ingestion. exposure: GGCX complexes with vitamin K, clotting-factor substrates and osteocalcin evidence_span: {"source_cache": "artifacts/k2-research/41290650.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0ea90e4c1af519fa0fc3645f4a4f8f0721924797e0eaa44569ff445c4afe19bc", "start_char": 0, "end_char": 1177, "text_sha256": "0ea90e4c1af519fa0fc3645f4a4f8f0721924797e0eaa44569ff445c4afe19bc"} [k2-p41290650] Structural insight into bicarbonate-mediated carboxylation by human vitamin K-dependent carboxylase. (2025). https://pubmed.ncbi.nlm.nih.gov/41290650/ DOI: 10.1038/s41467-025-65488-3
Complete structured claim and evidence
Cryo-EM structures and biochemical analyses supported a proposed bicarbonate-mediated carbon-dioxide capture model for GGCX.
Gamma-glutamyl carboxylase / GGCX → Carbon dioxide source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/41290650.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0ea90e4c1af519fa0fc3645f4a4f8f0721924797e0eaa44569ff445c4afe19bc", "start_char": 0, "end_char": 1177, "text_sha256": "0ea90e4c1af519fa0fc3645f4a4f8f0721924797e0eaa44569ff445c4afe19bc"}
experimental_model
Cryo-EM, mutagenesis and molecular dynamics
exposure
GGCX complexes with vitamin K, clotting-factor substrates and osteocalcin
limitations
The carbon-capture/proton-transfer sequence is the authors' structural mechanistic model, not a measured human dietary response or an established bicarbonate-supplement interaction.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Human GGCX
plain_language
The added chemical group comes from carbon dioxide; vitamin K supports the reaction rather than supplying the carbon.
primary_references
[k2-p41290650] Structural insight into bicarbonate-mediated carboxylation by human vitamin K-dependent carboxylase. (2025). https://pubmed.ncbi.nlm.nih.gov/41290650/ DOI: 10.1038/s41467-025-65488-3
tissue_or_cell_type
Substrate recognition and carbon-dioxide capture
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 422–433
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cryo-EM, mutagenesis and molecular dynamics · source_derived_draft · unverified_draft
### k2-ggcx-carbon-capture Cryo-EM structures and biochemical analyses supported a proposed bicarbonate-mediated carbon-dioxide capture model for GGCX. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The added chemical group comes from carbon dioxide; vitamin K supports the reaction rather than supplying the carbon. organism: Human GGCX tissue_or_cell_type: Substrate recognition and carbon-dioxide capture experimental_model: Cryo-EM, mutagenesis and molecular dynamics limitations: The carbon-capture/proton-transfer sequence is the authors' structural mechanistic model, not a measured human dietary response or an established bicarbonate-supplement interaction. exposure: GGCX complexes with vitamin K, clotting-factor substrates and osteocalcin evidence_span: {"source_cache": "artifacts/k2-research/41290650.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0ea90e4c1af519fa0fc3645f4a4f8f0721924797e0eaa44569ff445c4afe19bc", "start_char": 0, "end_char": 1177, "text_sha256": "0ea90e4c1af519fa0fc3645f4a4f8f0721924797e0eaa44569ff445c4afe19bc"} [k2-p41290650] Structural insight into bicarbonate-mediated carboxylation by human vitamin K-dependent carboxylase. (2025). https://pubmed.ncbi.nlm.nih.gov/41290650/ DOI: 10.1038/s41467-025-65488-3
Complete structured claim and evidence
Recombinantly expressed VKORC1 activity was sensitive to warfarin.
Warfarin → Human vitamin K epoxide reductase / VKORC1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/14765195.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "32f373fc0363ed079e580b2d47a3cb36c82b46871860fc6740b0285e23936496", "start_char": 0, "end_char": 1385, "text_sha256": "32f373fc0363ed079e580b2d47a3cb36c82b46871860fc6740b0285e23936496"}
experimental_model
siRNA identification and recombinant expression
exposure
Gene silencing, enzyme expression and warfarin sensitivity
limitations
Gene-discovery experiments; later structural understanding supersedes the original minimal topology description.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Human VKORC1 and insect-cell expression
plain_language
An anticoagulant acts on cofactor recycling, which changes protein maturation downstream.
primary_references
[k2-p14765195] Identification of the gene for vitamin K epoxide reductase. (2004). https://pubmed.ncbi.nlm.nih.gov/14765195/ DOI: 10.1038/nature02254
tissue_or_cell_type
Vitamin K recycling enzyme
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 448–459
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · siRNA identification and recombinant expression · source_derived_draft · unverified_draft
### k2-warfarin-vkor Recombinantly expressed VKORC1 activity was sensitive to warfarin. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: An anticoagulant acts on cofactor recycling, which changes protein maturation downstream. organism: Human VKORC1 and insect-cell expression tissue_or_cell_type: Vitamin K recycling enzyme experimental_model: siRNA identification and recombinant expression limitations: Gene-discovery experiments; later structural understanding supersedes the original minimal topology description. exposure: Gene silencing, enzyme expression and warfarin sensitivity evidence_span: {"source_cache": "artifacts/k2-research/14765195.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "32f373fc0363ed079e580b2d47a3cb36c82b46871860fc6740b0285e23936496", "start_char": 0, "end_char": 1385, "text_sha256": "32f373fc0363ed079e580b2d47a3cb36c82b46871860fc6740b0285e23936496"} [k2-p14765195] Identification of the gene for vitamin K epoxide reductase. (2004). https://pubmed.ncbi.nlm.nih.gov/14765195/ DOI: 10.1038/nature02254
Complete structured claim and evidence
Mgp-null mice developed arterial calcification leading to vascular rupture and death within two months.
Mouse matrix Gla protein / Mgp → Arterial calcification source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/k2-research/9052783.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3db0f618ff5c4f13affd3bb629c05ed69da28c837fc544848647afc9cfbfaf97", "start_char": 0, "end_char": 1199, "text_sha256": "3db0f618ff5c4f13affd3bb629c05ed69da28c837fc544848647afc9cfbfaf97"}
experimental_model
Targeted Mgp deletion
exposure
Mgp-null genotype
limitations
Loss of a protein is not isolated dietary K2 deficiency, and does not prove that extra K2 reverses established calcification.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Mice
plain_language
Soft tissues need active protection against inappropriate mineral deposition.
primary_references
[k2-p9052783] Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein. (1997). https://pubmed.ncbi.nlm.nih.gov/9052783/ DOI: 10.1038/386078a0
tissue_or_cell_type
Arteries and cartilage
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 461–472
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Targeted Mgp deletion · source_derived_draft · unverified_draft
### k2-mgp-arteries Mgp-null mice developed arterial calcification leading to vascular rupture and death within two months. Condition category: machinery_impairment nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Soft tissues need active protection against inappropriate mineral deposition. organism: Mice tissue_or_cell_type: Arteries and cartilage experimental_model: Targeted Mgp deletion limitations: Loss of a protein is not isolated dietary K2 deficiency, and does not prove that extra K2 reverses established calcification. exposure: Mgp-null genotype evidence_span: {"source_cache": "artifacts/k2-research/9052783.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3db0f618ff5c4f13affd3bb629c05ed69da28c837fc544848647afc9cfbfaf97", "start_char": 0, "end_char": 1199, "text_sha256": "3db0f618ff5c4f13affd3bb629c05ed69da28c837fc544848647afc9cfbfaf97"} [k2-p9052783] Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein. (1997). https://pubmed.ncbi.nlm.nih.gov/9052783/ DOI: 10.1038/386078a0
Complete structured claim and evidence
Mgp deletion caused inappropriate cartilage calcification with growth-plate abnormalities, short stature, osteopenia and fractures.
Mouse matrix Gla protein / Mgp → Bone mineralization source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/k2-research/9052783.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3db0f618ff5c4f13affd3bb629c05ed69da28c837fc544848647afc9cfbfaf97", "start_char": 0, "end_char": 1199, "text_sha256": "3db0f618ff5c4f13affd3bb629c05ed69da28c837fc544848647afc9cfbfaf97"}
experimental_model
Targeted Mgp deletion
exposure
Mgp-null genotype
limitations
Loss of a protein is not isolated dietary K2 deficiency, and does not prove that extra K2 reverses established calcification.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Mice
plain_language
Removing a calcification inhibitor did not simply make stronger bones.
primary_references
[k2-p9052783] Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein. (1997). https://pubmed.ncbi.nlm.nih.gov/9052783/ DOI: 10.1038/386078a0
tissue_or_cell_type
Arteries and cartilage
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 474–485
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Targeted Mgp deletion · source_derived_draft · unverified_draft
### k2-mgp-skeleton Mgp deletion caused inappropriate cartilage calcification with growth-plate abnormalities, short stature, osteopenia and fractures. Condition category: machinery_impairment nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Removing a calcification inhibitor did not simply make stronger bones. organism: Mice tissue_or_cell_type: Arteries and cartilage experimental_model: Targeted Mgp deletion limitations: Loss of a protein is not isolated dietary K2 deficiency, and does not prove that extra K2 reverses established calcification. exposure: Mgp-null genotype evidence_span: {"source_cache": "artifacts/k2-research/9052783.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3db0f618ff5c4f13affd3bb629c05ed69da28c837fc544848647afc9cfbfaf97", "start_char": 0, "end_char": 1199, "text_sha256": "3db0f618ff5c4f13affd3bb629c05ed69da28c837fc544848647afc9cfbfaf97"} [k2-p9052783] Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein. (1997). https://pubmed.ncbi.nlm.nih.gov/9052783/ DOI: 10.1038/386078a0
Complete structured claim and evidence
The double-knockout mice had reduced bone strength associated with disrupted mineral orientation, without a change in bone quantity in that study.
Mouse osteocalcin / Bglap → Bone mechanical strength source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/k2-research/32463816.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "287e43177fb9d632a2cba982f851b0a5a99d469761a1b2ad1e9e9e26933f850a", "start_char": 0, "end_char": 1082, "text_sha256": "287e43177fb9d632a2cba982f851b0a5a99d469761a1b2ad1e9e9e26933f850a"}
experimental_model
Bglap/Bglap2 double-deletion and skeletal analysis
exposure
Osteocalcin loss
limitations
Protein deletion rather than K2 restriction; endocrine findings in this mouse line cannot settle all osteocalcin hormone claims.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Mice
plain_language
Bone quantity and bone quality are different outcomes.
primary_references
[k2-p32463816] Osteocalcin is necessary for the alignment of apatite crystallites, but not glucose metabolism, testosterone synthesis, or muscle mass. (2020). https://pubmed.ncbi.nlm.nih.gov/32463816/ DOI: 10.1371/journal.pgen.1008586
tissue_or_cell_type
Bone mineral orientation and mechanical properties
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 500–511
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Bglap/Bglap2 double-deletion and skeletal analysis · source_derived_draft · unverified_draft
### k2-osteocalcin-strength The double-knockout mice had reduced bone strength associated with disrupted mineral orientation, without a change in bone quantity in that study. Condition category: machinery_impairment nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Bone quantity and bone quality are different outcomes. organism: Mice tissue_or_cell_type: Bone mineral orientation and mechanical properties experimental_model: Bglap/Bglap2 double-deletion and skeletal analysis limitations: Protein deletion rather than K2 restriction; endocrine findings in this mouse line cannot settle all osteocalcin hormone claims. exposure: Osteocalcin loss evidence_span: {"source_cache": "artifacts/k2-research/32463816.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "287e43177fb9d632a2cba982f851b0a5a99d469761a1b2ad1e9e9e26933f850a", "start_char": 0, "end_char": 1082, "text_sha256": "287e43177fb9d632a2cba982f851b0a5a99d469761a1b2ad1e9e9e26933f850a"} [k2-p32463816] Osteocalcin is necessary for the alignment of apatite crystallites, but not glucose metabolism, testosterone synthesis, or muscle mass. (2020). https://pubmed.ncbi.nlm.nih.gov/32463816/ DOI: 10.1371/journal.pgen.1008586
Complete structured claim and evidence
The phosphorylated serine motif also inhibited calcification and bound cell surfaces and vesicle-like structures.
Human matrix Gla protein / MGP → Vascular smooth muscle cell matrix calcification source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/17848178.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d2d79c43cc8142d6dc8f1eab4ac99b05ceb01e50e5afb41f5ca75aec732cba27", "start_char": 0, "end_char": 1745, "text_sha256": "d2d79c43cc8142d6dc8f1eab4ac99b05ceb01e50e5afb41f5ca75aec732cba27"}
experimental_model
Human vascular-cell calcification and synthetic-peptide assays
exposure
Elevated calcium, warfarin, K1 and modified MGP peptides
limitations
Vitamin K1 intervention in cells; K2-specific efficacy and human arterial reversal were not tested.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Human vascular smooth muscle cells
plain_language
Carboxylation is not the only modification contributing to MGP function.
primary_references
[k2-p17848178] Post-translational modifications regulate matrix Gla protein function: importance for inhibition of vascular smooth muscle cell calcification. (2007). https://pubmed.ncbi.nlm.nih.gov/17848178/ DOI: 10.1111/j.1538-7836.2007.02758.x
tissue_or_cell_type
Extracellular matrix and vesicle-like surfaces
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 526–537
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human vascular-cell calcification and synthetic-peptide assays · source_derived_draft · unverified_draft
### k2-mgp-phosphorylation The phosphorylated serine motif also inhibited calcification and bound cell surfaces and vesicle-like structures. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Carboxylation is not the only modification contributing to MGP function. organism: Human vascular smooth muscle cells tissue_or_cell_type: Extracellular matrix and vesicle-like surfaces experimental_model: Human vascular-cell calcification and synthetic-peptide assays limitations: Vitamin K1 intervention in cells; K2-specific efficacy and human arterial reversal were not tested. exposure: Elevated calcium, warfarin, K1 and modified MGP peptides evidence_span: {"source_cache": "artifacts/k2-research/17848178.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d2d79c43cc8142d6dc8f1eab4ac99b05ceb01e50e5afb41f5ca75aec732cba27", "start_char": 0, "end_char": 1745, "text_sha256": "d2d79c43cc8142d6dc8f1eab4ac99b05ceb01e50e5afb41f5ca75aec732cba27"} [k2-p17848178] Post-translational modifications regulate matrix Gla protein function: importance for inhibition of vascular smooth muscle cell calcification. (2007). https://pubmed.ncbi.nlm.nih.gov/17848178/ DOI: 10.1111/j.1538-7836.2007.02758.x
Complete structured claim and evidence
Warfarin-treated vascular cells produced uncarboxylated MGP and accumulated more calcium salts than controls.
Warfarin → Uncarboxylated matrix Gla protein source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/k2-research/17848178.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d2d79c43cc8142d6dc8f1eab4ac99b05ceb01e50e5afb41f5ca75aec732cba27", "start_char": 0, "end_char": 1745, "text_sha256": "d2d79c43cc8142d6dc8f1eab4ac99b05ceb01e50e5afb41f5ca75aec732cba27"}
experimental_model
Human vascular-cell calcification and synthetic-peptide assays
exposure
Elevated calcium, warfarin, K1 and modified MGP peptides
limitations
Vitamin K1 intervention in cells; K2-specific efficacy and human arterial reversal were not tested.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Human vascular smooth muscle cells
plain_language
Changing the vitamin K cycle changed the protein state and the mineral-deposition outcome in these cells.
primary_references
[k2-p17848178] Post-translational modifications regulate matrix Gla protein function: importance for inhibition of vascular smooth muscle cell calcification. (2007). https://pubmed.ncbi.nlm.nih.gov/17848178/ DOI: 10.1111/j.1538-7836.2007.02758.x
tissue_or_cell_type
Extracellular matrix and vesicle-like surfaces
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 539–550
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human vascular-cell calcification and synthetic-peptide assays · source_derived_draft · unverified_draft
### k2-warfarin-mgp Warfarin-treated vascular cells produced uncarboxylated MGP and accumulated more calcium salts than controls. Condition category: machinery_impairment nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Changing the vitamin K cycle changed the protein state and the mineral-deposition outcome in these cells. organism: Human vascular smooth muscle cells tissue_or_cell_type: Extracellular matrix and vesicle-like surfaces experimental_model: Human vascular-cell calcification and synthetic-peptide assays limitations: Vitamin K1 intervention in cells; K2-specific efficacy and human arterial reversal were not tested. exposure: Elevated calcium, warfarin, K1 and modified MGP peptides evidence_span: {"source_cache": "artifacts/k2-research/17848178.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d2d79c43cc8142d6dc8f1eab4ac99b05ceb01e50e5afb41f5ca75aec732cba27", "start_char": 0, "end_char": 1745, "text_sha256": "d2d79c43cc8142d6dc8f1eab4ac99b05ceb01e50e5afb41f5ca75aec732cba27"} [k2-p17848178] Post-translational modifications regulate matrix Gla protein function: importance for inhibition of vascular smooth muscle cell calcification. (2007). https://pubmed.ncbi.nlm.nih.gov/17848178/ DOI: 10.1111/j.1538-7836.2007.02758.x
Complete structured claim and evidence
MGP Gla residues and Pro64 contributed to BMP4 binding and inhibition; only BMP4-binding-competent variants prevented osteogenic differentiation and calcification.
Gamma-carboxylated matrix Gla protein → Human bone morphogenetic protein 4 / BMP4 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/18369157.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "34c7571f9f3a564647e458dc072113e807c277eaf5f542d6f3ab2e45f71ea5a4", "start_char": 0, "end_char": 1696, "text_sha256": "34c7571f9f3a564647e458dc072113e807c277eaf5f542d6f3ab2e45f71ea5a4"}
experimental_model
Site-directed mutants, calcium assays and BMP reporters
exposure
Gla and Pro64 alterations, calcium chelation and warfarin
limitations
Binding and calcification in experimental systems; systemic calcium should not be equated with a single binding-site measurement.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
MGP expression systems and calcifying vascular cells
plain_language
A calcium-binding protein also controls a signal that can change cell behavior.
primary_references
[k2-p18369157] Proline and gamma-carboxylated glutamate residues in matrix Gla protein are critical for binding of bone morphogenetic protein-4. (2008). https://pubmed.ncbi.nlm.nih.gov/18369157/ DOI: 10.1161/circresaha.107.166124
tissue_or_cell_type
Calcium/BMP binding and differentiation
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 552–563
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Site-directed mutants, calcium assays and BMP reporters · source_derived_draft · unverified_draft
### k2-mgp-bmp4 MGP Gla residues and Pro64 contributed to BMP4 binding and inhibition; only BMP4-binding-competent variants prevented osteogenic differentiation and calcification. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A calcium-binding protein also controls a signal that can change cell behavior. organism: MGP expression systems and calcifying vascular cells tissue_or_cell_type: Calcium/BMP binding and differentiation experimental_model: Site-directed mutants, calcium assays and BMP reporters limitations: Binding and calcification in experimental systems; systemic calcium should not be equated with a single binding-site measurement. exposure: Gla and Pro64 alterations, calcium chelation and warfarin evidence_span: {"source_cache": "artifacts/k2-research/18369157.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "34c7571f9f3a564647e458dc072113e807c277eaf5f542d6f3ab2e45f71ea5a4", "start_char": 0, "end_char": 1696, "text_sha256": "34c7571f9f3a564647e458dc072113e807c277eaf5f542d6f3ab2e45f71ea5a4"} [k2-p18369157] Proline and gamma-carboxylated glutamate residues in matrix Gla protein are critical for binding of bone morphogenetic protein-4. (2008). https://pubmed.ncbi.nlm.nih.gov/18369157/ DOI: 10.1161/circresaha.107.166124
Complete structured claim and evidence
Calcium chelation or warfarin treatment abolished MGP binding to BMP4 in the tested system.
Calcium ion → Human bone morphogenetic protein 4 / BMP4 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/18369157.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "34c7571f9f3a564647e458dc072113e807c277eaf5f542d6f3ab2e45f71ea5a4", "start_char": 0, "end_char": 1696, "text_sha256": "34c7571f9f3a564647e458dc072113e807c277eaf5f542d6f3ab2e45f71ea5a4"}
experimental_model
Site-directed mutants, calcium assays and BMP reporters
exposure
Gla and Pro64 alterations, calcium chelation and warfarin
limitations
Binding and calcification in experimental systems; systemic calcium should not be equated with a single binding-site measurement.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
MGP expression systems and calcifying vascular cells
plain_language
The calcium-binding and signaling functions were distinct but functionally connected.
primary_references
[k2-p18369157] Proline and gamma-carboxylated glutamate residues in matrix Gla protein are critical for binding of bone morphogenetic protein-4. (2008). https://pubmed.ncbi.nlm.nih.gov/18369157/ DOI: 10.1161/circresaha.107.166124
tissue_or_cell_type
Calcium/BMP binding and differentiation
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 565–576
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Site-directed mutants, calcium assays and BMP reporters · source_derived_draft · unverified_draft
### k2-mgp-calcium-dependency Calcium chelation or warfarin treatment abolished MGP binding to BMP4 in the tested system. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The calcium-binding and signaling functions were distinct but functionally connected. organism: MGP expression systems and calcifying vascular cells tissue_or_cell_type: Calcium/BMP binding and differentiation experimental_model: Site-directed mutants, calcium assays and BMP reporters limitations: Binding and calcification in experimental systems; systemic calcium should not be equated with a single binding-site measurement. exposure: Gla and Pro64 alterations, calcium chelation and warfarin evidence_span: {"source_cache": "artifacts/k2-research/18369157.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "34c7571f9f3a564647e458dc072113e807c277eaf5f542d6f3ab2e45f71ea5a4", "start_char": 0, "end_char": 1696, "text_sha256": "34c7571f9f3a564647e458dc072113e807c277eaf5f542d6f3ab2e45f71ea5a4"} [k2-p18369157] Proline and gamma-carboxylated glutamate residues in matrix Gla protein are critical for binding of bone morphogenetic protein-4. (2008). https://pubmed.ncbi.nlm.nih.gov/18369157/ DOI: 10.1161/circresaha.107.166124
Complete structured claim and evidence
Functional TYRO3 activation by GAS6 in the reporter system depended on vitamin K-mediated carboxylation and phosphatidylserine engagement.
Gamma-carboxylated human GAS6 → Human TYRO3 receptor tyrosine kinase source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/29176978.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "14dfae68318cd2654ee423539418eb489da66e26117e35473e99986b29b8efd7", "start_char": 0, "end_char": 1704, "text_sha256": "14dfae68318cd2654ee423539418eb489da66e26117e35473e99986b29b8efd7"}
experimental_model
TAM reporter cells and GAS6 domain/point mutagenesis
exposure
Warfarin, Gla/EGF mutations and PS-positive cells or vesicles
limitations
Receptor binding and receptor activation are different endpoints; no clinical K2 immune benefit was tested.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Recombinant human GAS6 and TAM reporter systems
plain_language
A modified signaling protein needs the right membrane surface to activate its receptor.
primary_references
[k2-p29176978] Requirement of Gamma-Carboxyglutamic Acid Modification and Phosphatidylserine Binding for the Activation of Tyro3, Axl, and Mertk Receptors by Growth Arrest-Specific 6. (2017). https://pubmed.ncbi.nlm.nih.gov/29176978/ DOI: 10.3389/fimmu.2017.01521
tissue_or_cell_type
Phosphatidylserine-bearing surfaces and receptors
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 578–589
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · TAM reporter cells and GAS6 domain/point mutagenesis · source_derived_draft · unverified_draft
### k2-gas6-tyro3 Functional TYRO3 activation by GAS6 in the reporter system depended on vitamin K-mediated carboxylation and phosphatidylserine engagement. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A modified signaling protein needs the right membrane surface to activate its receptor. organism: Recombinant human GAS6 and TAM reporter systems tissue_or_cell_type: Phosphatidylserine-bearing surfaces and receptors experimental_model: TAM reporter cells and GAS6 domain/point mutagenesis limitations: Receptor binding and receptor activation are different endpoints; no clinical K2 immune benefit was tested. exposure: Warfarin, Gla/EGF mutations and PS-positive cells or vesicles evidence_span: {"source_cache": "artifacts/k2-research/29176978.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "14dfae68318cd2654ee423539418eb489da66e26117e35473e99986b29b8efd7", "start_char": 0, "end_char": 1704, "text_sha256": "14dfae68318cd2654ee423539418eb489da66e26117e35473e99986b29b8efd7"} [k2-p29176978] Requirement of Gamma-Carboxyglutamic Acid Modification and Phosphatidylserine Binding for the Activation of Tyro3, Axl, and Mertk Receptors by Growth Arrest-Specific 6. (2017). https://pubmed.ncbi.nlm.nih.gov/29176978/ DOI: 10.3389/fimmu.2017.01521
Complete structured claim and evidence
Functional AXL activation by GAS6 in the reporter system depended on vitamin K-mediated carboxylation and phosphatidylserine engagement.
Gamma-carboxylated human GAS6 → Human AXL receptor tyrosine kinase source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/29176978.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "14dfae68318cd2654ee423539418eb489da66e26117e35473e99986b29b8efd7", "start_char": 0, "end_char": 1704, "text_sha256": "14dfae68318cd2654ee423539418eb489da66e26117e35473e99986b29b8efd7"}
experimental_model
TAM reporter cells and GAS6 domain/point mutagenesis
exposure
Warfarin, Gla/EGF mutations and PS-positive cells or vesicles
limitations
Receptor binding and receptor activation are different endpoints; no clinical K2 immune benefit was tested.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Recombinant human GAS6 and TAM reporter systems
plain_language
A modified signaling protein needs the right membrane surface to activate its receptor.
primary_references
[k2-p29176978] Requirement of Gamma-Carboxyglutamic Acid Modification and Phosphatidylserine Binding for the Activation of Tyro3, Axl, and Mertk Receptors by Growth Arrest-Specific 6. (2017). https://pubmed.ncbi.nlm.nih.gov/29176978/ DOI: 10.3389/fimmu.2017.01521
tissue_or_cell_type
Phosphatidylserine-bearing surfaces and receptors
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 591–602
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · TAM reporter cells and GAS6 domain/point mutagenesis · source_derived_draft · unverified_draft
### k2-gas6-axl Functional AXL activation by GAS6 in the reporter system depended on vitamin K-mediated carboxylation and phosphatidylserine engagement. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A modified signaling protein needs the right membrane surface to activate its receptor. organism: Recombinant human GAS6 and TAM reporter systems tissue_or_cell_type: Phosphatidylserine-bearing surfaces and receptors experimental_model: TAM reporter cells and GAS6 domain/point mutagenesis limitations: Receptor binding and receptor activation are different endpoints; no clinical K2 immune benefit was tested. exposure: Warfarin, Gla/EGF mutations and PS-positive cells or vesicles evidence_span: {"source_cache": "artifacts/k2-research/29176978.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "14dfae68318cd2654ee423539418eb489da66e26117e35473e99986b29b8efd7", "start_char": 0, "end_char": 1704, "text_sha256": "14dfae68318cd2654ee423539418eb489da66e26117e35473e99986b29b8efd7"} [k2-p29176978] Requirement of Gamma-Carboxyglutamic Acid Modification and Phosphatidylserine Binding for the Activation of Tyro3, Axl, and Mertk Receptors by Growth Arrest-Specific 6. (2017). https://pubmed.ncbi.nlm.nih.gov/29176978/ DOI: 10.3389/fimmu.2017.01521
Complete structured claim and evidence
Functional MERTK activation by GAS6 in the reporter system depended on vitamin K-mediated carboxylation and phosphatidylserine engagement.
Gamma-carboxylated human GAS6 → Human MERTK receptor tyrosine kinase source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/29176978.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "14dfae68318cd2654ee423539418eb489da66e26117e35473e99986b29b8efd7", "start_char": 0, "end_char": 1704, "text_sha256": "14dfae68318cd2654ee423539418eb489da66e26117e35473e99986b29b8efd7"}
experimental_model
TAM reporter cells and GAS6 domain/point mutagenesis
exposure
Warfarin, Gla/EGF mutations and PS-positive cells or vesicles
limitations
Receptor binding and receptor activation are different endpoints; no clinical K2 immune benefit was tested.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Recombinant human GAS6 and TAM reporter systems
plain_language
A modified signaling protein needs the right membrane surface to activate its receptor.
primary_references
[k2-p29176978] Requirement of Gamma-Carboxyglutamic Acid Modification and Phosphatidylserine Binding for the Activation of Tyro3, Axl, and Mertk Receptors by Growth Arrest-Specific 6. (2017). https://pubmed.ncbi.nlm.nih.gov/29176978/ DOI: 10.3389/fimmu.2017.01521
tissue_or_cell_type
Phosphatidylserine-bearing surfaces and receptors
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 604–615
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · TAM reporter cells and GAS6 domain/point mutagenesis · source_derived_draft · unverified_draft
### k2-gas6-mertk Functional MERTK activation by GAS6 in the reporter system depended on vitamin K-mediated carboxylation and phosphatidylserine engagement. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A modified signaling protein needs the right membrane surface to activate its receptor. organism: Recombinant human GAS6 and TAM reporter systems tissue_or_cell_type: Phosphatidylserine-bearing surfaces and receptors experimental_model: TAM reporter cells and GAS6 domain/point mutagenesis limitations: Receptor binding and receptor activation are different endpoints; no clinical K2 immune benefit was tested. exposure: Warfarin, Gla/EGF mutations and PS-positive cells or vesicles evidence_span: {"source_cache": "artifacts/k2-research/29176978.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "14dfae68318cd2654ee423539418eb489da66e26117e35473e99986b29b8efd7", "start_char": 0, "end_char": 1704, "text_sha256": "14dfae68318cd2654ee423539418eb489da66e26117e35473e99986b29b8efd7"} [k2-p29176978] Requirement of Gamma-Carboxyglutamic Acid Modification and Phosphatidylserine Binding for the Activation of Tyro3, Axl, and Mertk Receptors by Growth Arrest-Specific 6. (2017). https://pubmed.ncbi.nlm.nih.gov/29176978/ DOI: 10.3389/fimmu.2017.01521
Complete structured claim and evidence
Uncarboxylated GAS6 and selected domain-deletion variants retained TAM binding but acted as blocking decoy ligands rather than activators.
Uncarboxylated human GAS6 → TYRO3/AXL/MERTK receptor activation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/k2-research/29176978.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "14dfae68318cd2654ee423539418eb489da66e26117e35473e99986b29b8efd7", "start_char": 0, "end_char": 1704, "text_sha256": "14dfae68318cd2654ee423539418eb489da66e26117e35473e99986b29b8efd7"}
experimental_model
TAM reporter cells and GAS6 domain/point mutagenesis
exposure
Warfarin, Gla/EGF mutations and PS-positive cells or vesicles
limitations
Receptor binding and receptor activation are different endpoints; no clinical K2 immune benefit was tested.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Recombinant human GAS6 and TAM reporter systems
plain_language
The missing modification changed what happened after contact.
primary_references
[k2-p29176978] Requirement of Gamma-Carboxyglutamic Acid Modification and Phosphatidylserine Binding for the Activation of Tyro3, Axl, and Mertk Receptors by Growth Arrest-Specific 6. (2017). https://pubmed.ncbi.nlm.nih.gov/29176978/ DOI: 10.3389/fimmu.2017.01521
tissue_or_cell_type
Phosphatidylserine-bearing surfaces and receptors
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 617–628
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · TAM reporter cells and GAS6 domain/point mutagenesis · source_derived_draft · unverified_draft
### k2-gas6-decoy Uncarboxylated GAS6 and selected domain-deletion variants retained TAM binding but acted as blocking decoy ligands rather than activators. Condition category: machinery_impairment nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The missing modification changed what happened after contact. organism: Recombinant human GAS6 and TAM reporter systems tissue_or_cell_type: Phosphatidylserine-bearing surfaces and receptors experimental_model: TAM reporter cells and GAS6 domain/point mutagenesis limitations: Receptor binding and receptor activation are different endpoints; no clinical K2 immune benefit was tested. exposure: Warfarin, Gla/EGF mutations and PS-positive cells or vesicles evidence_span: {"source_cache": "artifacts/k2-research/29176978.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "14dfae68318cd2654ee423539418eb489da66e26117e35473e99986b29b8efd7", "start_char": 0, "end_char": 1704, "text_sha256": "14dfae68318cd2654ee423539418eb489da66e26117e35473e99986b29b8efd7"} [k2-p29176978] Requirement of Gamma-Carboxyglutamic Acid Modification and Phosphatidylserine Binding for the Activation of Tyro3, Axl, and Mertk Receptors by Growth Arrest-Specific 6. (2017). https://pubmed.ncbi.nlm.nih.gov/29176978/ DOI: 10.3389/fimmu.2017.01521
Complete structured claim and evidence
Osteoblast Ggcx deletion reduced multinucleated osteoclast formation and increased bone mass in six-month-old male mice.
Mouse gamma-glutamyl carboxylase / Ggcx → Osteoclast maturation and multinucleation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/k2-research/42045170.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "590b559787319a57a3e2fae4164fc2f2a40761ce653bd426d34a2d76aff5d4cf", "start_char": 0, "end_char": 1703, "text_sha256": "590b559787319a57a3e2fae4164fc2f2a40761ce653bd426d34a2d76aff5d4cf"}
experimental_model
Osteoblast-specific deletion, co-culture, receptor inhibitors and transgenic overexpression
exposure
Osteoblast Ggcx deletion; carboxylated GAS6 and AXL/MERTK perturbation
limitations
2026 mouse study; increased bone mass is not proven improved human bone quality, and no oral MK-7 regimen was tested.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Male mice and mouse osteoblast/osteoclast cultures
plain_language
Vitamin K-dependent signaling is part of bone remodeling, not a one-way instruction to deposit calcium.
primary_references
[k2-p42045170] Vitamin K-dependent carboxylation in osteoblasts regulates bone resorption through GAS6 in male mice. (2026). https://pubmed.ncbi.nlm.nih.gov/42045170/ DOI: 10.1038/s41413-026-00528-2
tissue_or_cell_type
Bone remodeling
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 630–641
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Osteoblast-specific deletion, co-culture, receptor inhibitors and transgenic overexpression · source_derived_draft · unverified_draft
### k2-ggcx-osteoclast Osteoblast Ggcx deletion reduced multinucleated osteoclast formation and increased bone mass in six-month-old male mice. Condition category: machinery_impairment nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin K-dependent signaling is part of bone remodeling, not a one-way instruction to deposit calcium. organism: Male mice and mouse osteoblast/osteoclast cultures tissue_or_cell_type: Bone remodeling experimental_model: Osteoblast-specific deletion, co-culture, receptor inhibitors and transgenic overexpression limitations: 2026 mouse study; increased bone mass is not proven improved human bone quality, and no oral MK-7 regimen was tested. exposure: Osteoblast Ggcx deletion; carboxylated GAS6 and AXL/MERTK perturbation evidence_span: {"source_cache": "artifacts/k2-research/42045170.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "590b559787319a57a3e2fae4164fc2f2a40761ce653bd426d34a2d76aff5d4cf", "start_char": 0, "end_char": 1703, "text_sha256": "590b559787319a57a3e2fae4164fc2f2a40761ce653bd426d34a2d76aff5d4cf"} [k2-p42045170] Vitamin K-dependent carboxylation in osteoblasts regulates bone resorption through GAS6 in male mice. (2026). https://pubmed.ncbi.nlm.nih.gov/42045170/ DOI: 10.1038/s41413-026-00528-2
Complete structured claim and evidence
Pharmacological inhibition of mouse-axl blocked osteoclast generation in the co-culture system.
Mouse Axl receptor tyrosine kinase → Osteoclast maturation and multinucleation source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/42045170.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "590b559787319a57a3e2fae4164fc2f2a40761ce653bd426d34a2d76aff5d4cf", "start_char": 0, "end_char": 1703, "text_sha256": "590b559787319a57a3e2fae4164fc2f2a40761ce653bd426d34a2d76aff5d4cf"}
experimental_model
Osteoblast-specific deletion, co-culture, receptor inhibitors and transgenic overexpression
exposure
Osteoblast Ggcx deletion; carboxylated GAS6 and AXL/MERTK perturbation
limitations
2026 mouse study; increased bone mass is not proven improved human bone quality, and no oral MK-7 regimen was tested.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Male mice and mouse osteoblast/osteoclast cultures
plain_language
The receptor is a separate intervention point in this pathway.
primary_references
[k2-p42045170] Vitamin K-dependent carboxylation in osteoblasts regulates bone resorption through GAS6 in male mice. (2026). https://pubmed.ncbi.nlm.nih.gov/42045170/ DOI: 10.1038/s41413-026-00528-2
tissue_or_cell_type
Bone remodeling
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 656–667
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Osteoblast-specific deletion, co-culture, receptor inhibitors and transgenic overexpression · source_derived_draft · unverified_draft
### k2-mouse-axl-osteoclast Pharmacological inhibition of mouse-axl blocked osteoclast generation in the co-culture system. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The receptor is a separate intervention point in this pathway. organism: Male mice and mouse osteoblast/osteoclast cultures tissue_or_cell_type: Bone remodeling experimental_model: Osteoblast-specific deletion, co-culture, receptor inhibitors and transgenic overexpression limitations: 2026 mouse study; increased bone mass is not proven improved human bone quality, and no oral MK-7 regimen was tested. exposure: Osteoblast Ggcx deletion; carboxylated GAS6 and AXL/MERTK perturbation evidence_span: {"source_cache": "artifacts/k2-research/42045170.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "590b559787319a57a3e2fae4164fc2f2a40761ce653bd426d34a2d76aff5d4cf", "start_char": 0, "end_char": 1703, "text_sha256": "590b559787319a57a3e2fae4164fc2f2a40761ce653bd426d34a2d76aff5d4cf"} [k2-p42045170] Vitamin K-dependent carboxylation in osteoblasts regulates bone resorption through GAS6 in male mice. (2026). https://pubmed.ncbi.nlm.nih.gov/42045170/ DOI: 10.1038/s41413-026-00528-2
Complete structured claim and evidence
Pharmacological inhibition of mouse-mertk blocked osteoclast generation in the co-culture system.
Mouse Mertk receptor tyrosine kinase → Osteoclast maturation and multinucleation source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/42045170.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "590b559787319a57a3e2fae4164fc2f2a40761ce653bd426d34a2d76aff5d4cf", "start_char": 0, "end_char": 1703, "text_sha256": "590b559787319a57a3e2fae4164fc2f2a40761ce653bd426d34a2d76aff5d4cf"}
experimental_model
Osteoblast-specific deletion, co-culture, receptor inhibitors and transgenic overexpression
exposure
Osteoblast Ggcx deletion; carboxylated GAS6 and AXL/MERTK perturbation
limitations
2026 mouse study; increased bone mass is not proven improved human bone quality, and no oral MK-7 regimen was tested.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Male mice and mouse osteoblast/osteoclast cultures
plain_language
The receptor is a separate intervention point in this pathway.
primary_references
[k2-p42045170] Vitamin K-dependent carboxylation in osteoblasts regulates bone resorption through GAS6 in male mice. (2026). https://pubmed.ncbi.nlm.nih.gov/42045170/ DOI: 10.1038/s41413-026-00528-2
tissue_or_cell_type
Bone remodeling
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 669–680
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Osteoblast-specific deletion, co-culture, receptor inhibitors and transgenic overexpression · source_derived_draft · unverified_draft
### k2-mouse-mertk-osteoclast Pharmacological inhibition of mouse-mertk blocked osteoclast generation in the co-culture system. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The receptor is a separate intervention point in this pathway. organism: Male mice and mouse osteoblast/osteoclast cultures tissue_or_cell_type: Bone remodeling experimental_model: Osteoblast-specific deletion, co-culture, receptor inhibitors and transgenic overexpression limitations: 2026 mouse study; increased bone mass is not proven improved human bone quality, and no oral MK-7 regimen was tested. exposure: Osteoblast Ggcx deletion; carboxylated GAS6 and AXL/MERTK perturbation evidence_span: {"source_cache": "artifacts/k2-research/42045170.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "590b559787319a57a3e2fae4164fc2f2a40761ce653bd426d34a2d76aff5d4cf", "start_char": 0, "end_char": 1703, "text_sha256": "590b559787319a57a3e2fae4164fc2f2a40761ce653bd426d34a2d76aff5d4cf"} [k2-p42045170] Vitamin K-dependent carboxylation in osteoblasts regulates bone resorption through GAS6 in male mice. (2026). https://pubmed.ncbi.nlm.nih.gov/42045170/ DOI: 10.1038/s41413-026-00528-2
Complete structured claim and evidence
Increasing marrow GAS6 in transgenic male mice increased osteoclast number and size and decreased bone mass.
Mouse growth arrest-specific protein 6 / Gas6 → Bone mass source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/42045170.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "590b559787319a57a3e2fae4164fc2f2a40761ce653bd426d34a2d76aff5d4cf", "start_char": 0, "end_char": 1703, "text_sha256": "590b559787319a57a3e2fae4164fc2f2a40761ce653bd426d34a2d76aff5d4cf"}
experimental_model
Osteoblast-specific deletion, co-culture, receptor inhibitors and transgenic overexpression
exposure
Osteoblast Ggcx deletion; carboxylated GAS6 and AXL/MERTK perturbation
limitations
2026 mouse study; increased bone mass is not proven improved human bone quality, and no oral MK-7 regimen was tested.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Male mice and mouse osteoblast/osteoclast cultures
plain_language
More of this signal changed the balance toward bone resorption in the mouse model.
primary_references
[k2-p42045170] Vitamin K-dependent carboxylation in osteoblasts regulates bone resorption through GAS6 in male mice. (2026). https://pubmed.ncbi.nlm.nih.gov/42045170/ DOI: 10.1038/s41413-026-00528-2
tissue_or_cell_type
Bone remodeling
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 682–693
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Osteoblast-specific deletion, co-culture, receptor inhibitors and transgenic overexpression · source_derived_draft · unverified_draft
### k2-gas6-bone-mass Increasing marrow GAS6 in transgenic male mice increased osteoclast number and size and decreased bone mass. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: More of this signal changed the balance toward bone resorption in the mouse model. organism: Male mice and mouse osteoblast/osteoclast cultures tissue_or_cell_type: Bone remodeling experimental_model: Osteoblast-specific deletion, co-culture, receptor inhibitors and transgenic overexpression limitations: 2026 mouse study; increased bone mass is not proven improved human bone quality, and no oral MK-7 regimen was tested. exposure: Osteoblast Ggcx deletion; carboxylated GAS6 and AXL/MERTK perturbation evidence_span: {"source_cache": "artifacts/k2-research/42045170.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "590b559787319a57a3e2fae4164fc2f2a40761ce653bd426d34a2d76aff5d4cf", "start_char": 0, "end_char": 1703, "text_sha256": "590b559787319a57a3e2fae4164fc2f2a40761ce653bd426d34a2d76aff5d4cf"} [k2-p42045170] Vitamin K-dependent carboxylation in osteoblasts regulates bone resorption through GAS6 in male mice. (2026). https://pubmed.ncbi.nlm.nih.gov/42045170/ DOI: 10.1038/s41413-026-00528-2
Complete structured claim and evidence
Vitamin K2 bound and activated human SXR and induced its CYP3A4 target gene in the tested system.
Vitamin K2 / menaquinone family → Human pregnane X receptor / SXR / PXR / NR1I2 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/12920130.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "073faa7585981854cba6f1544fbe593a19b98f2ba6b9aec02c32375171e46617", "start_char": 0, "end_char": 1589, "text_sha256": "073faa7585981854cba6f1544fbe593a19b98f2ba6b9aec02c32375171e46617"}
experimental_model
Ligand binding, gene expression and receptor-null mouse cells
exposure
Vitamin K2 exposure and receptor deficiency
limitations
Preclinical transcription effects; supplement-level target engagement in people is not established. Abstract calls the tested ligand K2 without distinguishing every homologue.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Human osteosarcoma cells and mouse calvarial cells
plain_language
K2 can have a receptor-signaling role separate from protein carboxylation.
primary_references
[k2-p12920130] Vitamin K2 regulation of bone homeostasis is mediated by the steroid and xenobiotic receptor SXR. (2003). https://pubmed.ncbi.nlm.nih.gov/12920130/ DOI: 10.1074/jbc.m303136200
tissue_or_cell_type
SXR/PXR transcription
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 695–706
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ligand binding, gene expression and receptor-null mouse cells · source_derived_draft · unverified_draft
### k2-k2-sxr Vitamin K2 bound and activated human SXR and induced its CYP3A4 target gene in the tested system. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: K2 can have a receptor-signaling role separate from protein carboxylation. organism: Human osteosarcoma cells and mouse calvarial cells tissue_or_cell_type: SXR/PXR transcription experimental_model: Ligand binding, gene expression and receptor-null mouse cells limitations: Preclinical transcription effects; supplement-level target engagement in people is not established. Abstract calls the tested ligand K2 without distinguishing every homologue. exposure: Vitamin K2 exposure and receptor deficiency evidence_span: {"source_cache": "artifacts/k2-research/12920130.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "073faa7585981854cba6f1544fbe593a19b98f2ba6b9aec02c32375171e46617", "start_char": 0, "end_char": 1589, "text_sha256": "073faa7585981854cba6f1544fbe593a19b98f2ba6b9aec02c32375171e46617"} [k2-p12920130] Vitamin K2 regulation of bone homeostasis is mediated by the steroid and xenobiotic receptor SXR. (2003). https://pubmed.ncbi.nlm.nih.gov/12920130/ DOI: 10.1074/jbc.m303136200
Complete structured claim and evidence
Vitamin K2 induced bone-marker expression in wild-type mouse calvarial cells but not Pxr-deficient cells.
Mouse pregnane X receptor / Pxr / Nr1i2 → Osteoblast marker gene expression source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/12920130.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "073faa7585981854cba6f1544fbe593a19b98f2ba6b9aec02c32375171e46617", "start_char": 0, "end_char": 1589, "text_sha256": "073faa7585981854cba6f1544fbe593a19b98f2ba6b9aec02c32375171e46617"}
experimental_model
Ligand binding, gene expression and receptor-null mouse cells
exposure
Vitamin K2 exposure and receptor deficiency
limitations
The measured outcome was expression of bone markers, not actual mineral deposition; loss of the mouse receptor need not predict human supplement response.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Human osteosarcoma cells and mouse calvarial cells
plain_language
The transcriptional response depended on the receptor in this model.
primary_references
[k2-p12920130] Vitamin K2 regulation of bone homeostasis is mediated by the steroid and xenobiotic receptor SXR. (2003). https://pubmed.ncbi.nlm.nih.gov/12920130/ DOI: 10.1074/jbc.m303136200
tissue_or_cell_type
SXR/PXR transcription
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 708–719
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ligand binding, gene expression and receptor-null mouse cells · source_derived_draft · unverified_draft
### k2-mouse-pxr-dependence Vitamin K2 induced bone-marker expression in wild-type mouse calvarial cells but not Pxr-deficient cells. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The transcriptional response depended on the receptor in this model. organism: Human osteosarcoma cells and mouse calvarial cells tissue_or_cell_type: SXR/PXR transcription experimental_model: Ligand binding, gene expression and receptor-null mouse cells limitations: The measured outcome was expression of bone markers, not actual mineral deposition; loss of the mouse receptor need not predict human supplement response. exposure: Vitamin K2 exposure and receptor deficiency evidence_span: {"source_cache": "artifacts/k2-research/12920130.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "073faa7585981854cba6f1544fbe593a19b98f2ba6b9aec02c32375171e46617", "start_char": 0, "end_char": 1589, "text_sha256": "073faa7585981854cba6f1544fbe593a19b98f2ba6b9aec02c32375171e46617"} [k2-p12920130] Vitamin K2 regulation of bone homeostasis is mediated by the steroid and xenobiotic receptor SXR. (2003). https://pubmed.ncbi.nlm.nih.gov/12920130/ DOI: 10.1074/jbc.m303136200
Complete structured claim and evidence
TSKU was identified as a primary SXR target responsive to vitamin K2 and rifampicin in osteoblastic cells.
Human pregnane X receptor / SXR / PXR / NR1I2 → Human tsukushi / TSKU source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/16606623.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a2c0e756d507fd0cef9dea48e3eedc193084378509ec54bce2c097f8491e4b45", "start_char": 0, "end_char": 1266, "text_sha256": "a2c0e756d507fd0cef9dea48e3eedc193084378509ec54bce2c097f8491e4b45"}
experimental_model
Microarray, qPCR and gain/loss-of-function studies
exposure
Vitamin K2 and rifampicin/SXR stimulation
limitations
Cell transcription and collagen accumulation; not a human fracture study.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Human osteoblastic MG63 cells
plain_language
The receptor connects to a separately identifiable downstream gene.
primary_references
[k2-p16606623] Steroid and xenobiotic receptor SXR mediates vitamin K2-activated transcription of extracellular matrix-related genes and collagen accumulation in osteoblastic cells. (2006). https://pubmed.ncbi.nlm.nih.gov/16606623/ DOI: 10.1074/jbc.m600896200
tissue_or_cell_type
Extracellular-matrix gene regulation
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 721–732
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Microarray, qPCR and gain/loss-of-function studies · source_derived_draft · unverified_draft
### k2-sxr-tsku TSKU was identified as a primary SXR target responsive to vitamin K2 and rifampicin in osteoblastic cells. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The receptor connects to a separately identifiable downstream gene. organism: Human osteoblastic MG63 cells tissue_or_cell_type: Extracellular-matrix gene regulation experimental_model: Microarray, qPCR and gain/loss-of-function studies limitations: Cell transcription and collagen accumulation; not a human fracture study. exposure: Vitamin K2 and rifampicin/SXR stimulation evidence_span: {"source_cache": "artifacts/k2-research/16606623.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a2c0e756d507fd0cef9dea48e3eedc193084378509ec54bce2c097f8491e4b45", "start_char": 0, "end_char": 1266, "text_sha256": "a2c0e756d507fd0cef9dea48e3eedc193084378509ec54bce2c097f8491e4b45"} [k2-p16606623] Steroid and xenobiotic receptor SXR mediates vitamin K2-activated transcription of extracellular matrix-related genes and collagen accumulation in osteoblastic cells. (2006). https://pubmed.ncbi.nlm.nih.gov/16606623/ DOI: 10.1074/jbc.m600896200
Complete structured claim and evidence
MATN2 was identified as a primary SXR target responsive to vitamin K2 and rifampicin in osteoblastic cells.
Human pregnane X receptor / SXR / PXR / NR1I2 → Human matrilin-2 / MATN2 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/16606623.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a2c0e756d507fd0cef9dea48e3eedc193084378509ec54bce2c097f8491e4b45", "start_char": 0, "end_char": 1266, "text_sha256": "a2c0e756d507fd0cef9dea48e3eedc193084378509ec54bce2c097f8491e4b45"}
experimental_model
Microarray, qPCR and gain/loss-of-function studies
exposure
Vitamin K2 and rifampicin/SXR stimulation
limitations
Cell transcription and collagen accumulation; not a human fracture study.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Human osteoblastic MG63 cells
plain_language
The receptor connects to a separately identifiable downstream gene.
primary_references
[k2-p16606623] Steroid and xenobiotic receptor SXR mediates vitamin K2-activated transcription of extracellular matrix-related genes and collagen accumulation in osteoblastic cells. (2006). https://pubmed.ncbi.nlm.nih.gov/16606623/ DOI: 10.1074/jbc.m600896200
tissue_or_cell_type
Extracellular-matrix gene regulation
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 734–745
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Microarray, qPCR and gain/loss-of-function studies · source_derived_draft · unverified_draft
### k2-sxr-matn2 MATN2 was identified as a primary SXR target responsive to vitamin K2 and rifampicin in osteoblastic cells. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The receptor connects to a separately identifiable downstream gene. organism: Human osteoblastic MG63 cells tissue_or_cell_type: Extracellular-matrix gene regulation experimental_model: Microarray, qPCR and gain/loss-of-function studies limitations: Cell transcription and collagen accumulation; not a human fracture study. exposure: Vitamin K2 and rifampicin/SXR stimulation evidence_span: {"source_cache": "artifacts/k2-research/16606623.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a2c0e756d507fd0cef9dea48e3eedc193084378509ec54bce2c097f8491e4b45", "start_char": 0, "end_char": 1266, "text_sha256": "a2c0e756d507fd0cef9dea48e3eedc193084378509ec54bce2c097f8491e4b45"} [k2-p16606623] Steroid and xenobiotic receptor SXR mediates vitamin K2-activated transcription of extracellular matrix-related genes and collagen accumulation in osteoblastic cells. (2006). https://pubmed.ncbi.nlm.nih.gov/16606623/ DOI: 10.1074/jbc.m600896200
Complete structured claim and evidence
CD14 was identified as a primary SXR target responsive to vitamin K2 and rifampicin in osteoblastic cells.
Human pregnane X receptor / SXR / PXR / NR1I2 → Human CD14 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/16606623.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a2c0e756d507fd0cef9dea48e3eedc193084378509ec54bce2c097f8491e4b45", "start_char": 0, "end_char": 1266, "text_sha256": "a2c0e756d507fd0cef9dea48e3eedc193084378509ec54bce2c097f8491e4b45"}
experimental_model
Microarray, qPCR and gain/loss-of-function studies
exposure
Vitamin K2 and rifampicin/SXR stimulation
limitations
Cell transcription and collagen accumulation; not a human fracture study.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Human osteoblastic MG63 cells
plain_language
The receptor connects to a separately identifiable downstream gene.
primary_references
[k2-p16606623] Steroid and xenobiotic receptor SXR mediates vitamin K2-activated transcription of extracellular matrix-related genes and collagen accumulation in osteoblastic cells. (2006). https://pubmed.ncbi.nlm.nih.gov/16606623/ DOI: 10.1074/jbc.m600896200
tissue_or_cell_type
Extracellular-matrix gene regulation
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 747–758
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Microarray, qPCR and gain/loss-of-function studies · source_derived_draft · unverified_draft
### k2-sxr-cd14 CD14 was identified as a primary SXR target responsive to vitamin K2 and rifampicin in osteoblastic cells. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The receptor connects to a separately identifiable downstream gene. organism: Human osteoblastic MG63 cells tissue_or_cell_type: Extracellular-matrix gene regulation experimental_model: Microarray, qPCR and gain/loss-of-function studies limitations: Cell transcription and collagen accumulation; not a human fracture study. exposure: Vitamin K2 and rifampicin/SXR stimulation evidence_span: {"source_cache": "artifacts/k2-research/16606623.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a2c0e756d507fd0cef9dea48e3eedc193084378509ec54bce2c097f8491e4b45", "start_char": 0, "end_char": 1266, "text_sha256": "a2c0e756d507fd0cef9dea48e3eedc193084378509ec54bce2c097f8491e4b45"} [k2-p16606623] Steroid and xenobiotic receptor SXR mediates vitamin K2-activated transcription of extracellular matrix-related genes and collagen accumulation in osteoblastic cells. (2006). https://pubmed.ncbi.nlm.nih.gov/16606623/ DOI: 10.1074/jbc.m600896200
Complete structured claim and evidence
Gain- and loss-of-function experiments implicated tsukushi in vitamin K2-associated collagen accumulation.
Human tsukushi / TSKU → Collagen accumulation in osteoblastic cells source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/16606623.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a2c0e756d507fd0cef9dea48e3eedc193084378509ec54bce2c097f8491e4b45", "start_char": 0, "end_char": 1266, "text_sha256": "a2c0e756d507fd0cef9dea48e3eedc193084378509ec54bce2c097f8491e4b45"}
experimental_model
Microarray, qPCR and gain/loss-of-function studies
exposure
Vitamin K2 and rifampicin/SXR stimulation
limitations
Cell transcription and collagen accumulation; not a human fracture study.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Human osteoblastic MG63 cells
plain_language
The pathway connects a receptor signal with assembly of the bone matrix.
primary_references
[k2-p16606623] Steroid and xenobiotic receptor SXR mediates vitamin K2-activated transcription of extracellular matrix-related genes and collagen accumulation in osteoblastic cells. (2006). https://pubmed.ncbi.nlm.nih.gov/16606623/ DOI: 10.1074/jbc.m600896200
tissue_or_cell_type
Extracellular-matrix gene regulation
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 760–771
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Microarray, qPCR and gain/loss-of-function studies · source_derived_draft · unverified_draft
### k2-tsku-collagen Gain- and loss-of-function experiments implicated tsukushi in vitamin K2-associated collagen accumulation. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The pathway connects a receptor signal with assembly of the bone matrix. organism: Human osteoblastic MG63 cells tissue_or_cell_type: Extracellular-matrix gene regulation experimental_model: Microarray, qPCR and gain/loss-of-function studies limitations: Cell transcription and collagen accumulation; not a human fracture study. exposure: Vitamin K2 and rifampicin/SXR stimulation evidence_span: {"source_cache": "artifacts/k2-research/16606623.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a2c0e756d507fd0cef9dea48e3eedc193084378509ec54bce2c097f8491e4b45", "start_char": 0, "end_char": 1266, "text_sha256": "a2c0e756d507fd0cef9dea48e3eedc193084378509ec54bce2c097f8491e4b45"} [k2-p16606623] Steroid and xenobiotic receptor SXR mediates vitamin K2-activated transcription of extracellular matrix-related genes and collagen accumulation in osteoblastic cells. (2006). https://pubmed.ncbi.nlm.nih.gov/16606623/ DOI: 10.1074/jbc.m600896200
Complete structured claim and evidence
Reduced vitamin K forms trapped radicals and inhibited phospholipid peroxidation in the tested systems.
Reduced vitamin K hydroquinone family → Lipid peroxidation source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/35922516.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3bd5750fd2d12a754ad4237018851391c6b5b80bac6ad58307321fb7c3042c5a", "start_char": 0, "end_char": 1403, "text_sha256": "3bd5750fd2d12a754ad4237018851391c6b5b80bac6ad58307321fb7c3042c5a"}
experimental_model
Enzyme/liposome chemistry, knockout cells and warfarin-exposed mice
exposure
MK-4/K1, NAD(P)H, FSP1 loss and inhibitors
limitations
Preclinical experiments; not a demonstrated oral MK-7 treatment for ferroptosis-related disease or a self-treatment regimen for anticoagulant poisoning.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Human recombinant FSP1, mammalian cells and mice
plain_language
The antioxidant action belongs to the reduced chemical form, not just the name on a supplement bottle.
primary_references
[k2-p35922516] A non-canonical vitamin K cycle is a potent ferroptosis suppressor. (2022). https://pubmed.ncbi.nlm.nih.gov/35922516/ DOI: 10.1038/s41586-022-05022-3
tissue_or_cell_type
Lipid peroxidation and vitamin K reduction
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 786–797
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Enzyme/liposome chemistry, knockout cells and warfarin-exposed mice · source_derived_draft · unverified_draft
### k2-kh2-lipid-protection Reduced vitamin K forms trapped radicals and inhibited phospholipid peroxidation in the tested systems. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The antioxidant action belongs to the reduced chemical form, not just the name on a supplement bottle. organism: Human recombinant FSP1, mammalian cells and mice tissue_or_cell_type: Lipid peroxidation and vitamin K reduction experimental_model: Enzyme/liposome chemistry, knockout cells and warfarin-exposed mice limitations: Preclinical experiments; not a demonstrated oral MK-7 treatment for ferroptosis-related disease or a self-treatment regimen for anticoagulant poisoning. exposure: MK-4/K1, NAD(P)H, FSP1 loss and inhibitors evidence_span: {"source_cache": "artifacts/k2-research/35922516.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3bd5750fd2d12a754ad4237018851391c6b5b80bac6ad58307321fb7c3042c5a", "start_char": 0, "end_char": 1403, "text_sha256": "3bd5750fd2d12a754ad4237018851391c6b5b80bac6ad58307321fb7c3042c5a"} [k2-p35922516] A non-canonical vitamin K cycle is a potent ferroptosis suppressor. (2022). https://pubmed.ncbi.nlm.nih.gov/35922516/ DOI: 10.1038/s41586-022-05022-3
Complete structured claim and evidence
FSP1 knockout diminished MK-4 and K1 protection; wild-type FSP1 rescued protection while its myristoylation-defective G2A mutant did not.
FSP1 / AIFM2 → Ferroptosis source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/k2-research/35922516.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a75e4881732cbe87173197db393b42d49fc6e8110df919fed8d63b16c9877da6", "start_char": 15449, "end_char": 16082, "text_sha256": "689a74e99dd668d48baef5232109dbf2898ba3adca2999a83a7bb24b321420c0"}
experimental_model
Enzyme/liposome chemistry, knockout cells and warfarin-exposed mice
exposure
MK-4/K1, NAD(P)H, FSP1 loss and inhibitors
limitations
Preclinical experiments; not a demonstrated oral MK-7 treatment for ferroptosis-related disease or a self-treatment regimen for anticoagulant poisoning.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Human recombinant FSP1, mammalian cells and mice
plain_language
Providing the quinone did not fully substitute for an appropriately located working reductase.
primary_references
[k2-p35922516] A non-canonical vitamin K cycle is a potent ferroptosis suppressor. (2022). https://pubmed.ncbi.nlm.nih.gov/35922516/ DOI: 10.1038/s41586-022-05022-3
tissue_or_cell_type
Lipid peroxidation and vitamin K reduction
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 799–810
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Enzyme/liposome chemistry, knockout cells and warfarin-exposed mice · source_derived_draft · unverified_draft
### k2-fsp1-loss FSP1 knockout diminished MK-4 and K1 protection; wild-type FSP1 rescued protection while its myristoylation-defective G2A mutant did not. Condition category: machinery_impairment nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Providing the quinone did not fully substitute for an appropriately located working reductase. organism: Human recombinant FSP1, mammalian cells and mice tissue_or_cell_type: Lipid peroxidation and vitamin K reduction experimental_model: Enzyme/liposome chemistry, knockout cells and warfarin-exposed mice limitations: Preclinical experiments; not a demonstrated oral MK-7 treatment for ferroptosis-related disease or a self-treatment regimen for anticoagulant poisoning. exposure: MK-4/K1, NAD(P)H, FSP1 loss and inhibitors evidence_span: {"source_cache": "artifacts/k2-research/35922516.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a75e4881732cbe87173197db393b42d49fc6e8110df919fed8d63b16c9877da6", "start_char": 15449, "end_char": 16082, "text_sha256": "689a74e99dd668d48baef5232109dbf2898ba3adca2999a83a7bb24b321420c0"} [k2-p35922516] A non-canonical vitamin K cycle is a potent ferroptosis suppressor. (2022). https://pubmed.ncbi.nlm.nih.gov/35922516/ DOI: 10.1038/s41586-022-05022-3
Complete structured claim and evidence
Cells lacking both GPX4 and FSP1 required higher K1/MK-4 concentrations to prevent ferroptosis than cells lacking GPX4 alone.
FSP1 / AIFM2 → Menaquinone-4 / MK-4 / menatetrenone source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/k2-research/35922516.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a75e4881732cbe87173197db393b42d49fc6e8110df919fed8d63b16c9877da6", "start_char": 16083, "end_char": 16259, "text_sha256": "942e81f7fca3a59aecc9d6cfcdc008e88931de54074e63eeb96c71af3d236eec"}
experimental_model
Enzyme/liposome chemistry, knockout cells and warfarin-exposed mice
exposure
MK-4/K1, NAD(P)H, FSP1 loss and inhibitors
limitations
Preclinical experiments; not a demonstrated oral MK-7 treatment for ferroptosis-related disease or a self-treatment regimen for anticoagulant poisoning.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Human recombinant FSP1, mammalian cells and mice
plain_language
The FSP1 pathway and selenium-dependent GPX4 defense are connected but not the same mechanism.
primary_references
[k2-p35922516] A non-canonical vitamin K cycle is a potent ferroptosis suppressor. (2022). https://pubmed.ncbi.nlm.nih.gov/35922516/ DOI: 10.1038/s41586-022-05022-3
tissue_or_cell_type
Lipid peroxidation and vitamin K reduction
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 812–823
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Enzyme/liposome chemistry, knockout cells and warfarin-exposed mice · source_derived_draft · unverified_draft
### k2-fsp1-gpx4-parallel Cells lacking both GPX4 and FSP1 required higher K1/MK-4 concentrations to prevent ferroptosis than cells lacking GPX4 alone. Condition category: machinery_impairment nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The FSP1 pathway and selenium-dependent GPX4 defense are connected but not the same mechanism. organism: Human recombinant FSP1, mammalian cells and mice tissue_or_cell_type: Lipid peroxidation and vitamin K reduction experimental_model: Enzyme/liposome chemistry, knockout cells and warfarin-exposed mice limitations: Preclinical experiments; not a demonstrated oral MK-7 treatment for ferroptosis-related disease or a self-treatment regimen for anticoagulant poisoning. exposure: MK-4/K1, NAD(P)H, FSP1 loss and inhibitors evidence_span: {"source_cache": "artifacts/k2-research/35922516.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a75e4881732cbe87173197db393b42d49fc6e8110df919fed8d63b16c9877da6", "start_char": 16083, "end_char": 16259, "text_sha256": "942e81f7fca3a59aecc9d6cfcdc008e88931de54074e63eeb96c71af3d236eec"} [k2-p35922516] A non-canonical vitamin K cycle is a potent ferroptosis suppressor. (2022). https://pubmed.ncbi.nlm.nih.gov/35922516/ DOI: 10.1038/s41586-022-05022-3
Complete structured claim and evidence
A CRISPR screen independently identified FSP1 as the warfarin-resistant vitamin K reductase; FSP1 inhibition impaired vitamin K-dependent carboxylation.
FSP1 / AIFM2 → Vitamin K-dependent protein gamma-carboxylation source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/36788244.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5fda09197d386351a1b1d261c9b385db36e02eab0c238bf18599d7086b501f93", "start_char": 0, "end_char": 1359, "text_sha256": "5fda09197d386351a1b1d261c9b385db36e02eab0c238bf18599d7086b501f93"}
experimental_model
Genome-wide CRISPR screen and reporter biochemistry
exposure
FSP1 knockout/inhibition and DHODH comparison
limitations
Supports cycle biochemistry; a different ferroptosis defense enzyme need not share the same vitamin K function.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Human vitamin K-dependent reporter cells
plain_language
The antioxidant enzyme also helps supply cofactor for protein modification.
primary_references
[k2-p36788244] A genome-wide CRISPR-Cas9 knockout screen identifies FSP1 as the warfarin-resistant vitamin K reductase. (2023). https://pubmed.ncbi.nlm.nih.gov/36788244/ DOI: 10.1038/s41467-023-36446-8
tissue_or_cell_type
Warfarin-resistant quinone reduction
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 825–836
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genome-wide CRISPR screen and reporter biochemistry · source_derived_draft · unverified_draft
### k2-fsp1-carboxylation A CRISPR screen independently identified FSP1 as the warfarin-resistant vitamin K reductase; FSP1 inhibition impaired vitamin K-dependent carboxylation. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The antioxidant enzyme also helps supply cofactor for protein modification. organism: Human vitamin K-dependent reporter cells tissue_or_cell_type: Warfarin-resistant quinone reduction experimental_model: Genome-wide CRISPR screen and reporter biochemistry limitations: Supports cycle biochemistry; a different ferroptosis defense enzyme need not share the same vitamin K function. exposure: FSP1 knockout/inhibition and DHODH comparison evidence_span: {"source_cache": "artifacts/k2-research/36788244.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5fda09197d386351a1b1d261c9b385db36e02eab0c238bf18599d7086b501f93", "start_char": 0, "end_char": 1359, "text_sha256": "5fda09197d386351a1b1d261c9b385db36e02eab0c238bf18599d7086b501f93"} [k2-p36788244] A genome-wide CRISPR-Cas9 knockout screen identifies FSP1 as the warfarin-resistant vitamin K reductase. (2023). https://pubmed.ncbi.nlm.nih.gov/36788244/ DOI: 10.1038/s41467-023-36446-8
Complete structured claim and evidence
DHODH did not support vitamin K-dependent carboxylation in the tested reporter system despite its separate ubiquinone-associated ferroptosis role.
Human dihydroorotate dehydrogenase / DHODH → Vitamin K-dependent protein gamma-carboxylation source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/36788244.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5fda09197d386351a1b1d261c9b385db36e02eab0c238bf18599d7086b501f93", "start_char": 0, "end_char": 1359, "text_sha256": "5fda09197d386351a1b1d261c9b385db36e02eab0c238bf18599d7086b501f93"}
experimental_model
Genome-wide CRISPR screen and reporter biochemistry
exposure
FSP1 knockout/inhibition and DHODH comparison
limitations
Supports cycle biochemistry; a different ferroptosis defense enzyme need not share the same vitamin K function.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Human vitamin K-dependent reporter cells
plain_language
Similar antioxidant roles do not make two enzymes interchangeable.
primary_references
[k2-p36788244] A genome-wide CRISPR-Cas9 knockout screen identifies FSP1 as the warfarin-resistant vitamin K reductase. (2023). https://pubmed.ncbi.nlm.nih.gov/36788244/ DOI: 10.1038/s41467-023-36446-8
tissue_or_cell_type
Warfarin-resistant quinone reduction
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 838–849
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genome-wide CRISPR screen and reporter biochemistry · source_derived_draft · unverified_draft
### k2-dhodh-not-k-reductase DHODH did not support vitamin K-dependent carboxylation in the tested reporter system despite its separate ubiquinone-associated ferroptosis role. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Similar antioxidant roles do not make two enzymes interchangeable. organism: Human vitamin K-dependent reporter cells tissue_or_cell_type: Warfarin-resistant quinone reduction experimental_model: Genome-wide CRISPR screen and reporter biochemistry limitations: Supports cycle biochemistry; a different ferroptosis defense enzyme need not share the same vitamin K function. exposure: FSP1 knockout/inhibition and DHODH comparison evidence_span: {"source_cache": "artifacts/k2-research/36788244.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5fda09197d386351a1b1d261c9b385db36e02eab0c238bf18599d7086b501f93", "start_char": 0, "end_char": 1359, "text_sha256": "5fda09197d386351a1b1d261c9b385db36e02eab0c238bf18599d7086b501f93"} [k2-p36788244] A genome-wide CRISPR-Cas9 knockout screen identifies FSP1 as the warfarin-resistant vitamin K reductase. (2023). https://pubmed.ncbi.nlm.nih.gov/36788244/ DOI: 10.1038/s41467-023-36446-8
Complete structured claim and evidence
The tested lipophilic statins inhibited UBIAD1 enzymatic activity in microsomal assays.
Human UBIAD1 prenyltransferase → Lipophilic statins studied in the UBIAD1 assay source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/25874989.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a3eb5f4c56ca7a3e70a32c020bba09f4fec5e91048b13a188017bf221f713a68", "start_char": 0, "end_char": 1777, "text_sha256": "a3eb5f4c56ca7a3e70a32c020bba09f4fec5e91048b13a188017bf221f713a68"}
experimental_model
Microsomal prenylation assays
exposure
Lipophilic statin exposure
limitations
Direct in-vitro inhibition; neither a clinical statin-to-K2-deficiency cascade nor a K2 supplementation indication is established.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Human UBIAD1 expressed in insect cells
plain_language
A drug-enzyme interaction is searchable without assuming it causes deficiency at usual treatment exposure.
primary_references
[k2-p25874989] Functional characterization of the vitamin K2 biosynthetic enzyme UBIAD1. (2015). https://pubmed.ncbi.nlm.nih.gov/25874989/ DOI: 10.1371/journal.pone.0125737
tissue_or_cell_type
MK-4 synthesis
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 851–862
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Microsomal prenylation assays · source_derived_draft · unverified_draft
### k2-ubiad-statin-context The tested lipophilic statins inhibited UBIAD1 enzymatic activity in microsomal assays. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A drug-enzyme interaction is searchable without assuming it causes deficiency at usual treatment exposure. organism: Human UBIAD1 expressed in insect cells tissue_or_cell_type: MK-4 synthesis experimental_model: Microsomal prenylation assays limitations: Direct in-vitro inhibition; neither a clinical statin-to-K2-deficiency cascade nor a K2 supplementation indication is established. exposure: Lipophilic statin exposure evidence_span: {"source_cache": "artifacts/k2-research/25874989.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a3eb5f4c56ca7a3e70a32c020bba09f4fec5e91048b13a188017bf221f713a68", "start_char": 0, "end_char": 1777, "text_sha256": "a3eb5f4c56ca7a3e70a32c020bba09f4fec5e91048b13a188017bf221f713a68"} [k2-p25874989] Functional characterization of the vitamin K2 biosynthetic enzyme UBIAD1. (2015). https://pubmed.ncbi.nlm.nih.gov/25874989/ DOI: 10.1371/journal.pone.0125737
Complete structured claim and evidence
Vitamin K2 transferred electrons in Drosophila mitochondria and improved ATP production; Heix-mutant defects were rescued by K2.
Vitamin K2 / menaquinone family → Mitochondrial respiratory electron transfer source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/k2-research/22582012.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1f7c8600fd883b912c1fd697b1bffb6e442e2763230347e5c198d88c0c6bb4cc", "start_char": 0, "end_char": 926, "text_sha256": "1f7c8600fd883b912c1fd697b1bffb6e442e2763230347e5c198d88c0c6bb4cc"}
experimental_model
Genetic modifier and mitochondrial function experiments
exposure
Heix/Pink1 defects and vitamin K2 rescue
limitations
Fly electron-transfer rescue does not establish replacement of human CoQ10 or treatment of Parkinson disease.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Drosophila
plain_language
An energy role was found in flies and is recorded with that species boundary.
primary_references
[k2-p22582012] Vitamin K2 is a mitochondrial electron carrier that rescues pink1 deficiency. (2012). https://pubmed.ncbi.nlm.nih.gov/22582012/ DOI: 10.1126/science.1218632
tissue_or_cell_type
Mitochondria
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 864–875
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genetic modifier and mitochondrial function experiments · source_derived_draft · unverified_draft
### k2-fly-mitochondria Vitamin K2 transferred electrons in Drosophila mitochondria and improved ATP production; Heix-mutant defects were rescued by K2. Condition category: machinery_impairment nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: An energy role was found in flies and is recorded with that species boundary. organism: Drosophila tissue_or_cell_type: Mitochondria experimental_model: Genetic modifier and mitochondrial function experiments limitations: Fly electron-transfer rescue does not establish replacement of human CoQ10 or treatment of Parkinson disease. exposure: Heix/Pink1 defects and vitamin K2 rescue evidence_span: {"source_cache": "artifacts/k2-research/22582012.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1f7c8600fd883b912c1fd697b1bffb6e442e2763230347e5c198d88c0c6bb4cc", "start_char": 0, "end_char": 926, "text_sha256": "1f7c8600fd883b912c1fd697b1bffb6e442e2763230347e5c198d88c0c6bb4cc"} [k2-p22582012] Vitamin K2 is a mitochondrial electron carrier that rescues pink1 deficiency. (2012). https://pubmed.ncbi.nlm.nih.gov/22582012/ DOI: 10.1126/science.1218632
Complete structured claim and evidence
Vitamin K2 entered mitochondria but restored neither respiratory electron flow nor ATP synthesis in CoQ-deficient human cells and yeast; CoQ4 did restore function.
Menaquinone-4 / MK-4 / menatetrenone → Mitochondrial respiratory electron transfer source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/k2-research/31024065.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "23cca3c157b598de639355c855be4221ce916ee9a338e2b59923fc980614281e", "start_char": 0, "end_char": 943, "text_sha256": "23cca3c157b598de639355c855be4221ce916ee9a338e2b59923fc980614281e"}
experimental_model
Cellular uptake and respiratory rescue comparisons
exposure
MK-4 versus CoQ4
limitations
Different organism and deficiency model from the fly study; failure here is a boundary to extrapolation, not a clerical error in either experiment.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Human CoQ10-deficient cell lines and CoQ6-deficient yeast
plain_language
Getting into the organelle did not make MK-4 a functional substitute for CoQ.
primary_references
[k2-p31024065] Vitamin K2 cannot substitute Coenzyme Q10 as electron carrier in the mitochondrial respiratory chain of mammalian cells. (2019). https://pubmed.ncbi.nlm.nih.gov/31024065/ DOI: 10.1038/s41598-019-43014-y
tissue_or_cell_type
Mitochondrial respiratory chain
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 877–888
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cellular uptake and respiratory rescue comparisons · source_derived_draft · unverified_draft
### k2-mk4-not-coq Vitamin K2 entered mitochondria but restored neither respiratory electron flow nor ATP synthesis in CoQ-deficient human cells and yeast; CoQ4 did restore function. Condition category: machinery_impairment nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Getting into the organelle did not make MK-4 a functional substitute for CoQ. organism: Human CoQ10-deficient cell lines and CoQ6-deficient yeast tissue_or_cell_type: Mitochondrial respiratory chain experimental_model: Cellular uptake and respiratory rescue comparisons limitations: Different organism and deficiency model from the fly study; failure here is a boundary to extrapolation, not a clerical error in either experiment. exposure: MK-4 versus CoQ4 evidence_span: {"source_cache": "artifacts/k2-research/31024065.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "23cca3c157b598de639355c855be4221ce916ee9a338e2b59923fc980614281e", "start_char": 0, "end_char": 943, "text_sha256": "23cca3c157b598de639355c855be4221ce916ee9a338e2b59923fc980614281e"} [k2-p31024065] Vitamin K2 cannot substitute Coenzyme Q10 as electron carrier in the mitochondrial respiratory chain of mammalian cells. (2019). https://pubmed.ncbi.nlm.nih.gov/31024065/ DOI: 10.1038/s41598-019-43014-y
Complete structured claim and evidence
Human VKORC1 missense variants were identified in combined vitamin K-dependent factor deficiency and in warfarin resistance; the deficiency variant did not increase VKOR activity upon overexpression.
Human vitamin K epoxide reductase / VKORC1 → Vitamin K-dependent coagulation protein function source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/k2-research/14765194.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e3691f9cae6d813e59dcad49c9715e4d93db1e6f46d16ec6399f12edb0502e1f", "start_char": 0, "end_char": 1293, "text_sha256": "e3691f9cae6d813e59dcad49c9715e4d93db1e6f46d16ec6399f12edb0502e1f"}
experimental_model
Human and rat genetic linkage with functional expression
exposure
Inherited deficiency/resistance variants
limitations
Rare genetic defects are different from dietary deficiency; historical multiprotein-complex language is not a current structural claim.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Human VKORC1 variants and rat resistance alleles
plain_language
Different variants affect either basal function or drug response.
primary_references
[k2-p14765194] Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. (2004). https://pubmed.ncbi.nlm.nih.gov/14765194/ DOI: 10.1038/nature02214
tissue_or_cell_type
Vitamin K recycling and coagulation
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 890–901
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human and rat genetic linkage with functional expression · source_derived_draft · unverified_draft
### k2-vkor-human-defect Human VKORC1 missense variants were identified in combined vitamin K-dependent factor deficiency and in warfarin resistance; the deficiency variant did not increase VKOR activity upon overexpression. Condition category: machinery_impairment nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Different variants affect either basal function or drug response. organism: Human VKORC1 variants and rat resistance alleles tissue_or_cell_type: Vitamin K recycling and coagulation experimental_model: Human and rat genetic linkage with functional expression limitations: Rare genetic defects are different from dietary deficiency; historical multiprotein-complex language is not a current structural claim. exposure: Inherited deficiency/resistance variants evidence_span: {"source_cache": "artifacts/k2-research/14765194.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e3691f9cae6d813e59dcad49c9715e4d93db1e6f46d16ec6399f12edb0502e1f", "start_char": 0, "end_char": 1293, "text_sha256": "e3691f9cae6d813e59dcad49c9715e4d93db1e6f46d16ec6399f12edb0502e1f"} [k2-p14765194] Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. (2004). https://pubmed.ncbi.nlm.nih.gov/14765194/ DOI: 10.1038/nature02214
Complete structured claim and evidence
Vkorc1-null mice died 2–20 days after birth with severe deficiency of carboxylated clotting factors and extensive hemorrhage.
Mouse vitamin K epoxide reductase / Vkorc1 → Hemorrhage source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/k2-research/19492146.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4f3957681861ebb8860b46b4a29e6b9c142ba79e7abff1af925dd48b7f0e0c6c", "start_char": 0, "end_char": 1237, "text_sha256": "4f3957681861ebb8860b46b4a29e6b9c142ba79e7abff1af925dd48b7f0e0c6c"}
experimental_model
Knockout and oral vitamin K rescue
exposure
Vkorc1 deletion
limitations
Shared vitamin K pathway; the rescue is not proof that K2 supplements replace medical management. Later alternative reductase findings prevent treating the paper as evidence that no bypass can exist.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Mice
plain_language
A major failure in the shared vitamin K cycle can become a clotting failure.
primary_references
[k2-p19492146] VKORC1 deficiency in mice causes early postnatal lethality due to severe bleeding. (2009). https://pubmed.ncbi.nlm.nih.gov/19492146/ DOI: 10.1160/th09-03-0204
tissue_or_cell_type
Postnatal coagulation and skeletal development
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 903–914
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Knockout and oral vitamin K rescue · source_derived_draft · unverified_draft
### k2-vkor-bleeding Vkorc1-null mice died 2–20 days after birth with severe deficiency of carboxylated clotting factors and extensive hemorrhage. Condition category: machinery_impairment nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A major failure in the shared vitamin K cycle can become a clotting failure. organism: Mice tissue_or_cell_type: Postnatal coagulation and skeletal development experimental_model: Knockout and oral vitamin K rescue limitations: Shared vitamin K pathway; the rescue is not proof that K2 supplements replace medical management. Later alternative reductase findings prevent treating the paper as evidence that no bypass can exist. exposure: Vkorc1 deletion evidence_span: {"source_cache": "artifacts/k2-research/19492146.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4f3957681861ebb8860b46b4a29e6b9c142ba79e7abff1af925dd48b7f0e0c6c", "start_char": 0, "end_char": 1237, "text_sha256": "4f3957681861ebb8860b46b4a29e6b9c142ba79e7abff1af925dd48b7f0e0c6c"} [k2-p19492146] VKORC1 deficiency in mice causes early postnatal lethality due to severe bleeding. (2009). https://pubmed.ncbi.nlm.nih.gov/19492146/ DOI: 10.1160/th09-03-0204
Complete structured claim and evidence
Oral vitamin K rescued the lethal bleeding phenotype of Vkorc1-null mice.
Vitamin K → Hemorrhage source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/k2-research/19492146.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4f3957681861ebb8860b46b4a29e6b9c142ba79e7abff1af925dd48b7f0e0c6c", "start_char": 0, "end_char": 1237, "text_sha256": "4f3957681861ebb8860b46b4a29e6b9c142ba79e7abff1af925dd48b7f0e0c6c"}
experimental_model
Knockout and oral vitamin K rescue
exposure
Vkorc1 deletion
limitations
Shared vitamin K pathway; the rescue is not proof that K2 supplements replace medical management. Later alternative reductase findings prevent treating the paper as evidence that no bypass can exist.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Mice
plain_language
Cofactor supply could bypass enough of the defect in this experimental model.
primary_references
[k2-p19492146] VKORC1 deficiency in mice causes early postnatal lethality due to severe bleeding. (2009). https://pubmed.ncbi.nlm.nih.gov/19492146/ DOI: 10.1160/th09-03-0204
tissue_or_cell_type
Postnatal coagulation and skeletal development
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 916–927
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Knockout and oral vitamin K rescue · source_derived_draft · unverified_draft
### k2-vkor-rescue Oral vitamin K rescued the lethal bleeding phenotype of Vkorc1-null mice. Condition category: machinery_impairment nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Cofactor supply could bypass enough of the defect in this experimental model. organism: Mice tissue_or_cell_type: Postnatal coagulation and skeletal development experimental_model: Knockout and oral vitamin K rescue limitations: Shared vitamin K pathway; the rescue is not proof that K2 supplements replace medical management. Later alternative reductase findings prevent treating the paper as evidence that no bypass can exist. exposure: Vkorc1 deletion evidence_span: {"source_cache": "artifacts/k2-research/19492146.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4f3957681861ebb8860b46b4a29e6b9c142ba79e7abff1af925dd48b7f0e0c6c", "start_char": 0, "end_char": 1237, "text_sha256": "4f3957681861ebb8860b46b4a29e6b9c142ba79e7abff1af925dd48b7f0e0c6c"} [k2-p19492146] VKORC1 deficiency in mice causes early postnatal lethality due to severe bleeding. (2009). https://pubmed.ncbi.nlm.nih.gov/19492146/ DOI: 10.1160/th09-03-0204
Complete structured claim and evidence
The GGCX case had combined vitamin K-dependent factor deficiency; vitamin K substitution only partly normalized factor levels.
Gamma-glutamyl carboxylase / GGCX → Vitamin K-dependent coagulation protein function source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/k2-research/15287948.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "76e5cf58ebc717968ad3ae32a76aec9f05e783468666181042dfb8989805dadf", "start_char": 0, "end_char": 1069, "text_sha256": "76e5cf58ebc717968ad3ae32a76aec9f05e783468666181042dfb8989805dadf"}
experimental_model
Human compound-heterozygous GGCX case and mutation analysis
exposure
Splice-site and Arg485Pro variants; vitamin K substitution
limitations
Single rare genetic case; the suspected binding-site mechanism was proposed, not established by structure.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Human patient
plain_language
The nutrient cannot necessarily repair the protein that uses it.
primary_references
[k2-p15287948] Compound heterozygous mutations in the gamma-glutamyl carboxylase gene cause combined deficiency of all vitamin K-dependent blood coagulation factors. (2004). https://pubmed.ncbi.nlm.nih.gov/15287948/ DOI: 10.1111/j.1365-2141.2004.05071.x
tissue_or_cell_type
Vitamin K-dependent coagulation proteins
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 929–940
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human compound-heterozygous GGCX case and mutation analysis · source_derived_draft · unverified_draft
### k2-ggcx-factor-defect The GGCX case had combined vitamin K-dependent factor deficiency; vitamin K substitution only partly normalized factor levels. Condition category: machinery_impairment nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The nutrient cannot necessarily repair the protein that uses it. organism: Human patient tissue_or_cell_type: Vitamin K-dependent coagulation proteins experimental_model: Human compound-heterozygous GGCX case and mutation analysis limitations: Single rare genetic case; the suspected binding-site mechanism was proposed, not established by structure. exposure: Splice-site and Arg485Pro variants; vitamin K substitution evidence_span: {"source_cache": "artifacts/k2-research/15287948.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "76e5cf58ebc717968ad3ae32a76aec9f05e783468666181042dfb8989805dadf", "start_char": 0, "end_char": 1069, "text_sha256": "76e5cf58ebc717968ad3ae32a76aec9f05e783468666181042dfb8989805dadf"} [k2-p15287948] Compound heterozygous mutations in the gamma-glutamyl carboxylase gene cause combined deficiency of all vitamin K-dependent blood coagulation factors. (2004). https://pubmed.ncbi.nlm.nih.gov/15287948/ DOI: 10.1111/j.1365-2141.2004.05071.x
Complete structured claim and evidence
The tested bovine-f2 Gla-domain protein showed calcium-specific contact with negatively charged phospholipid monolayers.
Bovine prothrombin / F2 → Phosphatidylserine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/9609692.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d29ed548c28e5a8015742351c50aa94c8853d0f1846794964b67a73324c879bd", "start_char": 0, "end_char": 2064, "text_sha256": "d29ed548c28e5a8015742351c50aa94c8853d0f1846794964b67a73324c879bd"}
experimental_model
Protein adsorption to model phospholipid monolayers
exposure
Phosphatidylserine-containing monolayers
limitations
Model membrane binding, not whole-blood thrombosis. Species remain distinct.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Purified human and bovine proteins
plain_language
Carboxylation supports a protein surface that interacts with calcium and membranes.
primary_references
[k2-p9609692] Adsorption of vitamin K-dependent blood coagulation proteins to spread phospholipid monolayers as determined from combined measurements of the surface pressure and surface protein concentration. (1998). https://pubmed.ncbi.nlm.nih.gov/9609692/ DOI: 10.1021/bi973118+
tissue_or_cell_type
Calcium-dependent Gla-domain membrane contact
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 942–953
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Protein adsorption to model phospholipid monolayers · source_derived_draft · unverified_draft
### k2-membrane-bovine-f2 The tested bovine-f2 Gla-domain protein showed calcium-specific contact with negatively charged phospholipid monolayers. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Carboxylation supports a protein surface that interacts with calcium and membranes. organism: Purified human and bovine proteins tissue_or_cell_type: Calcium-dependent Gla-domain membrane contact experimental_model: Protein adsorption to model phospholipid monolayers limitations: Model membrane binding, not whole-blood thrombosis. Species remain distinct. exposure: Phosphatidylserine-containing monolayers evidence_span: {"source_cache": "artifacts/k2-research/9609692.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d29ed548c28e5a8015742351c50aa94c8853d0f1846794964b67a73324c879bd", "start_char": 0, "end_char": 2064, "text_sha256": "d29ed548c28e5a8015742351c50aa94c8853d0f1846794964b67a73324c879bd"} [k2-p9609692] Adsorption of vitamin K-dependent blood coagulation proteins to spread phospholipid monolayers as determined from combined measurements of the surface pressure and surface protein concentration. (1998). https://pubmed.ncbi.nlm.nih.gov/9609692/ DOI: 10.1021/bi973118+
Complete structured claim and evidence
The tested f9 Gla-domain protein showed calcium-specific contact with negatively charged phospholipid monolayers.
Human coagulation factor IX / F9 → Phosphatidylserine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/9609692.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d29ed548c28e5a8015742351c50aa94c8853d0f1846794964b67a73324c879bd", "start_char": 0, "end_char": 2064, "text_sha256": "d29ed548c28e5a8015742351c50aa94c8853d0f1846794964b67a73324c879bd"}
experimental_model
Protein adsorption to model phospholipid monolayers
exposure
Phosphatidylserine-containing monolayers
limitations
Model membrane binding, not whole-blood thrombosis. Species remain distinct.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Purified human and bovine proteins
plain_language
Carboxylation supports a protein surface that interacts with calcium and membranes.
primary_references
[k2-p9609692] Adsorption of vitamin K-dependent blood coagulation proteins to spread phospholipid monolayers as determined from combined measurements of the surface pressure and surface protein concentration. (1998). https://pubmed.ncbi.nlm.nih.gov/9609692/ DOI: 10.1021/bi973118+
tissue_or_cell_type
Calcium-dependent Gla-domain membrane contact
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 955–966
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Protein adsorption to model phospholipid monolayers · source_derived_draft · unverified_draft
### k2-membrane-f9 The tested f9 Gla-domain protein showed calcium-specific contact with negatively charged phospholipid monolayers. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Carboxylation supports a protein surface that interacts with calcium and membranes. organism: Purified human and bovine proteins tissue_or_cell_type: Calcium-dependent Gla-domain membrane contact experimental_model: Protein adsorption to model phospholipid monolayers limitations: Model membrane binding, not whole-blood thrombosis. Species remain distinct. exposure: Phosphatidylserine-containing monolayers evidence_span: {"source_cache": "artifacts/k2-research/9609692.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d29ed548c28e5a8015742351c50aa94c8853d0f1846794964b67a73324c879bd", "start_char": 0, "end_char": 2064, "text_sha256": "d29ed548c28e5a8015742351c50aa94c8853d0f1846794964b67a73324c879bd"} [k2-p9609692] Adsorption of vitamin K-dependent blood coagulation proteins to spread phospholipid monolayers as determined from combined measurements of the surface pressure and surface protein concentration. (1998). https://pubmed.ncbi.nlm.nih.gov/9609692/ DOI: 10.1021/bi973118+
Complete structured claim and evidence
The tested pros1 Gla-domain protein showed calcium-specific contact with negatively charged phospholipid monolayers.
Human protein S / PROS1 → Phosphatidylserine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/9609692.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d29ed548c28e5a8015742351c50aa94c8853d0f1846794964b67a73324c879bd", "start_char": 0, "end_char": 2064, "text_sha256": "d29ed548c28e5a8015742351c50aa94c8853d0f1846794964b67a73324c879bd"}
experimental_model
Protein adsorption to model phospholipid monolayers
exposure
Phosphatidylserine-containing monolayers
limitations
Model membrane binding, not whole-blood thrombosis. Species remain distinct.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Purified human and bovine proteins
plain_language
Carboxylation supports a protein surface that interacts with calcium and membranes.
primary_references
[k2-p9609692] Adsorption of vitamin K-dependent blood coagulation proteins to spread phospholipid monolayers as determined from combined measurements of the surface pressure and surface protein concentration. (1998). https://pubmed.ncbi.nlm.nih.gov/9609692/ DOI: 10.1021/bi973118+
tissue_or_cell_type
Calcium-dependent Gla-domain membrane contact
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 968–979
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Protein adsorption to model phospholipid monolayers · source_derived_draft · unverified_draft
### k2-membrane-pros1 The tested pros1 Gla-domain protein showed calcium-specific contact with negatively charged phospholipid monolayers. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Carboxylation supports a protein surface that interacts with calcium and membranes. organism: Purified human and bovine proteins tissue_or_cell_type: Calcium-dependent Gla-domain membrane contact experimental_model: Protein adsorption to model phospholipid monolayers limitations: Model membrane binding, not whole-blood thrombosis. Species remain distinct. exposure: Phosphatidylserine-containing monolayers evidence_span: {"source_cache": "artifacts/k2-research/9609692.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d29ed548c28e5a8015742351c50aa94c8853d0f1846794964b67a73324c879bd", "start_char": 0, "end_char": 2064, "text_sha256": "d29ed548c28e5a8015742351c50aa94c8853d0f1846794964b67a73324c879bd"} [k2-p9609692] Adsorption of vitamin K-dependent blood coagulation proteins to spread phospholipid monolayers as determined from combined measurements of the surface pressure and surface protein concentration. (1998). https://pubmed.ncbi.nlm.nih.gov/9609692/ DOI: 10.1021/bi973118+
Complete structured claim and evidence
The tested bovine-proc Gla-domain protein showed calcium-specific contact with negatively charged phospholipid monolayers.
Bovine protein C / PROC → Phosphatidylserine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/9609692.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d29ed548c28e5a8015742351c50aa94c8853d0f1846794964b67a73324c879bd", "start_char": 0, "end_char": 2064, "text_sha256": "d29ed548c28e5a8015742351c50aa94c8853d0f1846794964b67a73324c879bd"}
experimental_model
Protein adsorption to model phospholipid monolayers
exposure
Phosphatidylserine-containing monolayers
limitations
Model membrane binding, not whole-blood thrombosis. Species remain distinct.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Purified human and bovine proteins
plain_language
Carboxylation supports a protein surface that interacts with calcium and membranes.
primary_references
[k2-p9609692] Adsorption of vitamin K-dependent blood coagulation proteins to spread phospholipid monolayers as determined from combined measurements of the surface pressure and surface protein concentration. (1998). https://pubmed.ncbi.nlm.nih.gov/9609692/ DOI: 10.1021/bi973118+
tissue_or_cell_type
Calcium-dependent Gla-domain membrane contact
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 981–992
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Protein adsorption to model phospholipid monolayers · source_derived_draft · unverified_draft
### k2-membrane-bovine-proc The tested bovine-proc Gla-domain protein showed calcium-specific contact with negatively charged phospholipid monolayers. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Carboxylation supports a protein surface that interacts with calcium and membranes. organism: Purified human and bovine proteins tissue_or_cell_type: Calcium-dependent Gla-domain membrane contact experimental_model: Protein adsorption to model phospholipid monolayers limitations: Model membrane binding, not whole-blood thrombosis. Species remain distinct. exposure: Phosphatidylserine-containing monolayers evidence_span: {"source_cache": "artifacts/k2-research/9609692.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d29ed548c28e5a8015742351c50aa94c8853d0f1846794964b67a73324c879bd", "start_char": 0, "end_char": 2064, "text_sha256": "d29ed548c28e5a8015742351c50aa94c8853d0f1846794964b67a73324c879bd"} [k2-p9609692] Adsorption of vitamin K-dependent blood coagulation proteins to spread phospholipid monolayers as determined from combined measurements of the surface pressure and surface protein concentration. (1998). https://pubmed.ncbi.nlm.nih.gov/9609692/ DOI: 10.1021/bi973118+
Complete structured claim and evidence
The tested proc Gla-domain protein showed calcium-specific contact with negatively charged phospholipid monolayers.
Human protein C / PROC → Phosphatidylserine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/9609692.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d29ed548c28e5a8015742351c50aa94c8853d0f1846794964b67a73324c879bd", "start_char": 0, "end_char": 2064, "text_sha256": "d29ed548c28e5a8015742351c50aa94c8853d0f1846794964b67a73324c879bd"}
experimental_model
Protein adsorption to model phospholipid monolayers
exposure
Phosphatidylserine-containing monolayers
limitations
Model membrane binding, not whole-blood thrombosis. Species remain distinct.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Purified human and bovine proteins
plain_language
Carboxylation supports a protein surface that interacts with calcium and membranes.
primary_references
[k2-p9609692] Adsorption of vitamin K-dependent blood coagulation proteins to spread phospholipid monolayers as determined from combined measurements of the surface pressure and surface protein concentration. (1998). https://pubmed.ncbi.nlm.nih.gov/9609692/ DOI: 10.1021/bi973118+
tissue_or_cell_type
Calcium-dependent Gla-domain membrane contact
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 994–1005
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Protein adsorption to model phospholipid monolayers · source_derived_draft · unverified_draft
### k2-membrane-proc The tested proc Gla-domain protein showed calcium-specific contact with negatively charged phospholipid monolayers. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Carboxylation supports a protein surface that interacts with calcium and membranes. organism: Purified human and bovine proteins tissue_or_cell_type: Calcium-dependent Gla-domain membrane contact experimental_model: Protein adsorption to model phospholipid monolayers limitations: Model membrane binding, not whole-blood thrombosis. Species remain distinct. exposure: Phosphatidylserine-containing monolayers evidence_span: {"source_cache": "artifacts/k2-research/9609692.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d29ed548c28e5a8015742351c50aa94c8853d0f1846794964b67a73324c879bd", "start_char": 0, "end_char": 2064, "text_sha256": "d29ed548c28e5a8015742351c50aa94c8853d0f1846794964b67a73324c879bd"} [k2-p9609692] Adsorption of vitamin K-dependent blood coagulation proteins to spread phospholipid monolayers as determined from combined measurements of the surface pressure and surface protein concentration. (1998). https://pubmed.ncbi.nlm.nih.gov/9609692/ DOI: 10.1021/bi973118+
Complete structured claim and evidence
Prothrombin carboxylation normalized at 200 micrograms/day, whereas other vitamin K markers had not all returned to baseline after short repletion up to 450 micrograms/day.
Phylloquinone → Vitamin K-dependent protein gamma-carboxylation source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/k2-research/12888638.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c57beda0b2c7bdc471fd6f4bfa926e9f12846f040c95689648f599d6cceae874", "start_char": 0, "end_char": 1461, "text_sha256": "c57beda0b2c7bdc471fd6f4bfa926e9f12846f040c95689648f599d6cceae874"}
experimental_model
Metabolic-unit dietary depletion/repletion
exposure
K1 restricted to 18 micrograms/day for 28 days, then stepped repletion
limitations
K1 restriction probes shared vitamin K status, not an isolated dietary K2 requirement. Biochemical undercarboxylation is not equivalent to clinical bleeding or fractures.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
21 women aged 60–80 years
plain_language
A liver-related marker can recover before an extrahepatic marker.
primary_references
[k2-p12888638] Dietary phylloquinone depletion and repletion in older women. (2003). https://pubmed.ncbi.nlm.nih.gov/12888638/ DOI: 10.1093/jn/133.8.2565
tissue_or_cell_type
Hepatic and extrahepatic protein markers
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 1020–1031
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Metabolic-unit dietary depletion/repletion · source_derived_draft · unverified_draft
### k2-different-repletion Prothrombin carboxylation normalized at 200 micrograms/day, whereas other vitamin K markers had not all returned to baseline after short repletion up to 450 micrograms/day. Condition category: nutrient_deficiency nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A liver-related marker can recover before an extrahepatic marker. organism: 21 women aged 60–80 years tissue_or_cell_type: Hepatic and extrahepatic protein markers experimental_model: Metabolic-unit dietary depletion/repletion limitations: K1 restriction probes shared vitamin K status, not an isolated dietary K2 requirement. Biochemical undercarboxylation is not equivalent to clinical bleeding or fractures. exposure: K1 restricted to 18 micrograms/day for 28 days, then stepped repletion evidence_span: {"source_cache": "artifacts/k2-research/12888638.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c57beda0b2c7bdc471fd6f4bfa926e9f12846f040c95689648f599d6cceae874", "start_char": 0, "end_char": 1461, "text_sha256": "c57beda0b2c7bdc471fd6f4bfa926e9f12846f040c95689648f599d6cceae874"} [k2-p12888638] Dietary phylloquinone depletion and repletion in older women. (2003). https://pubmed.ncbi.nlm.nih.gov/12888638/ DOI: 10.1093/jn/133.8.2565
Complete structured claim and evidence
Acenocoumarol increased uncarboxylated factor II, osteocalcin and dp-ucMGP and reduced endogenous thrombin generation.
Acenocoumarol → Undercarboxylated prothrombin / PIVKA-II source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/k2-research/23530987.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "95455ea6f2fc6de10ed4d46cad9c1587c004ccd445d7b08066108261f161e6af", "start_char": 0, "end_char": 1740, "text_sha256": "95455ea6f2fc6de10ed4d46cad9c1587c004ccd445d7b08066108261f161e6af"}
experimental_model
Sequential dose-response intervention during anticoagulation
exposure
Acenocoumarol followed by MK-7 10, 20 and 45 micrograms/day
limitations
Small pharmacological study; no dose here is a recommended safe self-adjustment. Drug was acenocoumarol, not warfarin.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
18 healthy adults; 15 attained target INR
plain_language
The drug changed several proteins that share the same vitamin K cycle.
primary_references
[k2-p23530987] Effect of low-dose supplements of menaquinone-7 (vitamin K2 ) on the stability of oral anticoagulant treatment: dose-response relationship in healthy volunteers. (2013). https://pubmed.ncbi.nlm.nih.gov/23530987/ DOI: 10.1111/jth.12203
tissue_or_cell_type
Coagulation, osteocalcin and MGP markers
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 1033–1044
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Sequential dose-response intervention during anticoagulation · source_derived_draft · unverified_draft
### k2-acenocoumarol-markers Acenocoumarol increased uncarboxylated factor II, osteocalcin and dp-ucMGP and reduced endogenous thrombin generation. Condition category: machinery_impairment nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The drug changed several proteins that share the same vitamin K cycle. organism: 18 healthy adults; 15 attained target INR tissue_or_cell_type: Coagulation, osteocalcin and MGP markers experimental_model: Sequential dose-response intervention during anticoagulation limitations: Small pharmacological study; no dose here is a recommended safe self-adjustment. Drug was acenocoumarol, not warfarin. exposure: Acenocoumarol followed by MK-7 10, 20 and 45 micrograms/day evidence_span: {"source_cache": "artifacts/k2-research/23530987.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "95455ea6f2fc6de10ed4d46cad9c1587c004ccd445d7b08066108261f161e6af", "start_char": 0, "end_char": 1740, "text_sha256": "95455ea6f2fc6de10ed4d46cad9c1587c004ccd445d7b08066108261f161e6af"} [k2-p23530987] Effect of low-dose supplements of menaquinone-7 (vitamin K2 ) on the stability of oral anticoagulant treatment: dose-response relationship in healthy volunteers. (2013). https://pubmed.ncbi.nlm.nih.gov/23530987/ DOI: 10.1111/jth.12203
Complete structured claim and evidence
MK-7 at 10 and 20 micrograms/day increased endogenous thrombin potential by approximately 20% and 30%, respectively; ucOC and dp-ucMGP did not change.
Menaquinone-7 / MK-7 → Endogenous thrombin generation potential source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/k2-research/23530987.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "95455ea6f2fc6de10ed4d46cad9c1587c004ccd445d7b08066108261f161e6af", "start_char": 0, "end_char": 1740, "text_sha256": "95455ea6f2fc6de10ed4d46cad9c1587c004ccd445d7b08066108261f161e6af"}
experimental_model
Sequential dose-response intervention during anticoagulation
exposure
Acenocoumarol followed by MK-7 10, 20 and 45 micrograms/day
limitations
Small pharmacological study; no dose here is a recommended safe self-adjustment. Drug was acenocoumarol, not warfarin.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
18 healthy adults; 15 attained target INR
plain_language
A clotting response appeared without the same response in the other measured proteins.
primary_references
[k2-p23530987] Effect of low-dose supplements of menaquinone-7 (vitamin K2 ) on the stability of oral anticoagulant treatment: dose-response relationship in healthy volunteers. (2013). https://pubmed.ncbi.nlm.nih.gov/23530987/ DOI: 10.1111/jth.12203
tissue_or_cell_type
Coagulation, osteocalcin and MGP markers
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 1059–1070
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Sequential dose-response intervention during anticoagulation · source_derived_draft · unverified_draft
### k2-mk7-thrombin MK-7 at 10 and 20 micrograms/day increased endogenous thrombin potential by approximately 20% and 30%, respectively; ucOC and dp-ucMGP did not change. Condition category: machinery_impairment nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A clotting response appeared without the same response in the other measured proteins. organism: 18 healthy adults; 15 attained target INR tissue_or_cell_type: Coagulation, osteocalcin and MGP markers experimental_model: Sequential dose-response intervention during anticoagulation limitations: Small pharmacological study; no dose here is a recommended safe self-adjustment. Drug was acenocoumarol, not warfarin. exposure: Acenocoumarol followed by MK-7 10, 20 and 45 micrograms/day evidence_span: {"source_cache": "artifacts/k2-research/23530987.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "95455ea6f2fc6de10ed4d46cad9c1587c004ccd445d7b08066108261f161e6af", "start_char": 0, "end_char": 1740, "text_sha256": "95455ea6f2fc6de10ed4d46cad9c1587c004ccd445d7b08066108261f161e6af"} [k2-p23530987] Effect of low-dose supplements of menaquinone-7 (vitamin K2 ) on the stability of oral anticoagulant treatment: dose-response relationship in healthy volunteers. (2013). https://pubmed.ncbi.nlm.nih.gov/23530987/ DOI: 10.1111/jth.12203
Complete structured claim and evidence
MK-7 reduced age-related loss of lumbar-spine and femoral-neck BMD/BMC, but not total-hip BMD, over three years.
Menaquinone-7 / MK-7 → Lumbar spine bone mineral density source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/23525894.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a3ce7b3935f14513cb967410370b1bca786c7548989964d658077108e362f4dc", "start_char": 0, "end_char": 2060, "text_sha256": "a3ce7b3935f14513cb967410370b1bca786c7548989964d658077108e362f4dc"}
experimental_model
Three-year double-blind placebo-controlled trial
exposure
MK-7 180 micrograms/day
limitations
Site-specific surrogate outcomes; not proof of fracture prevention in every population. The arterial-stiffness publication describes the same cohort.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
244 healthy postmenopausal women
plain_language
The result differed by skeletal site.
primary_references
[k2-p23525894] Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women. (2013). https://pubmed.ncbi.nlm.nih.gov/23525894/ DOI: 10.1007/s00198-013-2325-6
tissue_or_cell_type
DXA and osteocalcin markers
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 1072–1083
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Three-year double-blind placebo-controlled trial · source_derived_draft · unverified_draft
### k2-mk7-bone-positive MK-7 reduced age-related loss of lumbar-spine and femoral-neck BMD/BMC, but not total-hip BMD, over three years. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The result differed by skeletal site. organism: 244 healthy postmenopausal women tissue_or_cell_type: DXA and osteocalcin markers experimental_model: Three-year double-blind placebo-controlled trial limitations: Site-specific surrogate outcomes; not proof of fracture prevention in every population. The arterial-stiffness publication describes the same cohort. exposure: MK-7 180 micrograms/day evidence_span: {"source_cache": "artifacts/k2-research/23525894.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a3ce7b3935f14513cb967410370b1bca786c7548989964d658077108e362f4dc", "start_char": 0, "end_char": 2060, "text_sha256": "a3ce7b3935f14513cb967410370b1bca786c7548989964d658077108e362f4dc"} [k2-p23525894] Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women. (2013). https://pubmed.ncbi.nlm.nih.gov/23525894/ DOI: 10.1007/s00198-013-2325-6
Complete structured claim and evidence
With calcium and D3 in both groups, MK-7 reduced ucOC by about 65% after one year.
Menaquinone-7 / MK-7 → Undercarboxylated osteocalcin source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Adding menatetrenone to calcium did not significantly reduce new vertebral fractures in the full analysis set; the clinical-fracture secondary difference was also nonsignificant.
Menaquinone-4 / MK-4 / menatetrenone → New vertebral fracture incidence source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/19082528.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6d29b8f43348d8acd6ee85d4f65bb0cdd1352dd6f5113f58d7e58d7196bd96f5", "start_char": 0, "end_char": 1657, "text_sha256": "6d29b8f43348d8acd6ee85d4f65bb0cdd1352dd6f5113f58d7e58d7196bd96f5"}
experimental_model
Randomized open-label trial with blinded endpoint evaluation
exposure
Calcium alone versus calcium plus menatetrenone; 36-month primary and 48-month secondary endpoints
limitations
Full-analysis null result; advanced-osteoporosis subgroup signals are exploratory and do not replace the overall endpoint.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
4378 osteoporotic postmenopausal women
plain_language
A large trial did not establish a general fracture-prevention benefit from adding MK-4.
primary_references
[k2-p19082528] Randomized controlled study on the prevention of osteoporotic fractures (OF study): a phase IV clinical study of 15-mg menatetrenone capsules. (2009). https://pubmed.ncbi.nlm.nih.gov/19082528/ DOI: 10.1007/s00774-008-0008-8
tissue_or_cell_type
Vertebral and clinical fractures
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 1111–1122
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized open-label trial with blinded endpoint evaluation · source_derived_draft · unverified_draft
### k2-mk4-fractures-null Adding menatetrenone to calcium did not significantly reduce new vertebral fractures in the full analysis set; the clinical-fracture secondary difference was also nonsignificant. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A large trial did not establish a general fracture-prevention benefit from adding MK-4. organism: 4378 osteoporotic postmenopausal women tissue_or_cell_type: Vertebral and clinical fractures experimental_model: Randomized open-label trial with blinded endpoint evaluation limitations: Full-analysis null result; advanced-osteoporosis subgroup signals are exploratory and do not replace the overall endpoint. exposure: Calcium alone versus calcium plus menatetrenone; 36-month primary and 48-month secondary endpoints evidence_span: {"source_cache": "artifacts/k2-research/19082528.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6d29b8f43348d8acd6ee85d4f65bb0cdd1352dd6f5113f58d7e58d7196bd96f5", "start_char": 0, "end_char": 1657, "text_sha256": "6d29b8f43348d8acd6ee85d4f65bb0cdd1352dd6f5113f58d7e58d7196bd96f5"} [k2-p19082528] Randomized controlled study on the prevention of osteoporotic fractures (OF study): a phase IV clinical study of 15-mg menatetrenone capsules. (2009). https://pubmed.ncbi.nlm.nih.gov/19082528/ DOI: 10.1007/s00774-008-0008-8
Complete structured claim and evidence
MK-7 produced greater one-third distal-radius BMD loss than placebo: change difference -0.023 g/cm2, 95% CI -0.039 to -0.008.
Menaquinone-7 / MK-7 → One-third distal radius bone mineral density source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/36460034.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7a8ad2542116a1ddc804eead1694c7057dfaff243eacb993c6c39745e73264a0", "start_char": 0, "end_char": 1754, "text_sha256": "7a8ad2542116a1ddc804eead1694c7057dfaff243eacb993c6c39745e73264a0"}
experimental_model
Two-year randomized double-blind RenaKvit trial
exposure
MK-7 360 micrograms/day versus placebo
limitations
Kidney-disease context and substantial attrition; site-specific findings cannot be condensed into universal bone benefit or harm.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
123 chronic-dialysis patients randomized
plain_language
One skeletal site had a worse result despite improved vitamin K markers.
primary_references
[k2-p36460034] Vitamin K supplementation and bone mineral density in dialysis: results of the double-blind, randomized, placebo-controlled RenaKvit trial. (2023). https://pubmed.ncbi.nlm.nih.gov/36460034/ DOI: 10.1093/ndt/gfac315
tissue_or_cell_type
Site-specific BMD
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 1124–1135
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two-year randomized double-blind RenaKvit trial · source_derived_draft · unverified_draft
### k2-dialysis-radius MK-7 produced greater one-third distal-radius BMD loss than placebo: change difference -0.023 g/cm2, 95% CI -0.039 to -0.008. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: One skeletal site had a worse result despite improved vitamin K markers. organism: 123 chronic-dialysis patients randomized tissue_or_cell_type: Site-specific BMD experimental_model: Two-year randomized double-blind RenaKvit trial limitations: Kidney-disease context and substantial attrition; site-specific findings cannot be condensed into universal bone benefit or harm. exposure: MK-7 360 micrograms/day versus placebo evidence_span: {"source_cache": "artifacts/k2-research/36460034.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7a8ad2542116a1ddc804eead1694c7057dfaff243eacb993c6c39745e73264a0", "start_char": 0, "end_char": 1754, "text_sha256": "7a8ad2542116a1ddc804eead1694c7057dfaff243eacb993c6c39745e73264a0"} [k2-p36460034] Vitamin K supplementation and bone mineral density in dialysis: results of the double-blind, randomized, placebo-controlled RenaKvit trial. (2023). https://pubmed.ncbi.nlm.nih.gov/36460034/ DOI: 10.1093/ndt/gfac315
Complete structured claim and evidence
Lumbar-spine BMD was preserved relative to placebo: change difference 0.050 g/cm2, 95% CI 0.015–0.085; other measured sites had no significant effect.
Menaquinone-7 / MK-7 → Lumbar spine bone mineral density source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/36460034.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7a8ad2542116a1ddc804eead1694c7057dfaff243eacb993c6c39745e73264a0", "start_char": 0, "end_char": 1754, "text_sha256": "7a8ad2542116a1ddc804eead1694c7057dfaff243eacb993c6c39745e73264a0"}
experimental_model
Two-year randomized double-blind RenaKvit trial
exposure
MK-7 360 micrograms/day versus placebo
limitations
Kidney-disease context and substantial attrition; site-specific findings cannot be condensed into universal bone benefit or harm.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
123 chronic-dialysis patients randomized
plain_language
A different skeletal site in the same trial had a favorable result.
primary_references
[k2-p36460034] Vitamin K supplementation and bone mineral density in dialysis: results of the double-blind, randomized, placebo-controlled RenaKvit trial. (2023). https://pubmed.ncbi.nlm.nih.gov/36460034/ DOI: 10.1093/ndt/gfac315
tissue_or_cell_type
Site-specific BMD
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 1137–1148
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two-year randomized double-blind RenaKvit trial · source_derived_draft · unverified_draft
### k2-dialysis-spine Lumbar-spine BMD was preserved relative to placebo: change difference 0.050 g/cm2, 95% CI 0.015–0.085; other measured sites had no significant effect. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A different skeletal site in the same trial had a favorable result. organism: 123 chronic-dialysis patients randomized tissue_or_cell_type: Site-specific BMD experimental_model: Two-year randomized double-blind RenaKvit trial limitations: Kidney-disease context and substantial attrition; site-specific findings cannot be condensed into universal bone benefit or harm. exposure: MK-7 360 micrograms/day versus placebo evidence_span: {"source_cache": "artifacts/k2-research/36460034.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7a8ad2542116a1ddc804eead1694c7057dfaff243eacb993c6c39745e73264a0", "start_char": 0, "end_char": 1754, "text_sha256": "7a8ad2542116a1ddc804eead1694c7057dfaff243eacb993c6c39745e73264a0"} [k2-p36460034] Vitamin K supplementation and bone mineral density in dialysis: results of the double-blind, randomized, placebo-controlled RenaKvit trial. (2023). https://pubmed.ncbi.nlm.nih.gov/36460034/ DOI: 10.1093/ndt/gfac315
Complete structured claim and evidence
MK-7 improved carotid-femoral pulse-wave velocity and stiffness index in the full group; several additional measures improved in those with higher baseline stiffness.
Menaquinone-7 / MK-7 → Arterial stiffness source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/25694037.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "744049d613c87cb18fd3fe9cf3d7242e3c424a8d463900701bee102d4072b8e3", "start_char": 0, "end_char": 1822, "text_sha256": "744049d613c87cb18fd3fe9cf3d7242e3c424a8d463900701bee102d4072b8e3"}
experimental_model
Three-year randomized double-blind trial
exposure
MK-7 180 micrograms/day
limitations
Same cohort as the bone publication; stiffness is not CT calcification or cardiovascular-event incidence.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
244 healthy postmenopausal women
plain_language
A vessel-mechanics outcome improved in this selected population.
primary_references
[k2-p25694037] Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women. A double-blind randomised clinical trial. (2015). https://pubmed.ncbi.nlm.nih.gov/25694037/ DOI: 10.1160/th14-08-0675
tissue_or_cell_type
Arterial stiffness and circulating proteins
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 1150–1161
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Three-year randomized double-blind trial · source_derived_draft · unverified_draft
### k2-mk7-stiffness MK-7 improved carotid-femoral pulse-wave velocity and stiffness index in the full group; several additional measures improved in those with higher baseline stiffness. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A vessel-mechanics outcome improved in this selected population. organism: 244 healthy postmenopausal women tissue_or_cell_type: Arterial stiffness and circulating proteins experimental_model: Three-year randomized double-blind trial limitations: Same cohort as the bone publication; stiffness is not CT calcification or cardiovascular-event incidence. exposure: MK-7 180 micrograms/day evidence_span: {"source_cache": "artifacts/k2-research/25694037.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "744049d613c87cb18fd3fe9cf3d7242e3c424a8d463900701bee102d4072b8e3", "start_char": 0, "end_char": 1822, "text_sha256": "744049d613c87cb18fd3fe9cf3d7242e3c424a8d463900701bee102d4072b8e3"} [k2-p25694037] Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women. A double-blind randomised clinical trial. (2015). https://pubmed.ncbi.nlm.nih.gov/25694037/ DOI: 10.1160/th14-08-0675
Complete structured claim and evidence
MK-7 reduced dp-ucMGP by about 50% but did not change the measured acute-phase or endothelial-dysfunction markers.
Menaquinone-7 / MK-7 → Dephosphorylated uncarboxylated matrix Gla protein source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/25694037.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "744049d613c87cb18fd3fe9cf3d7242e3c424a8d463900701bee102d4072b8e3", "start_char": 0, "end_char": 1822, "text_sha256": "744049d613c87cb18fd3fe9cf3d7242e3c424a8d463900701bee102d4072b8e3"}
experimental_model
Three-year randomized double-blind trial
exposure
MK-7 180 micrograms/day
limitations
Same cohort as the bone publication; stiffness is not CT calcification or cardiovascular-event incidence.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
244 healthy postmenopausal women
plain_language
Different blood markers responded differently.
primary_references
[k2-p25694037] Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women. A double-blind randomised clinical trial. (2015). https://pubmed.ncbi.nlm.nih.gov/25694037/ DOI: 10.1160/th14-08-0675
tissue_or_cell_type
Arterial stiffness and circulating proteins
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 1163–1174
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Three-year randomized double-blind trial · source_derived_draft · unverified_draft
### k2-mk7-dpucmgp MK-7 reduced dp-ucMGP by about 50% but did not change the measured acute-phase or endothelial-dysfunction markers. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Different blood markers responded differently. organism: 244 healthy postmenopausal women tissue_or_cell_type: Arterial stiffness and circulating proteins experimental_model: Three-year randomized double-blind trial limitations: Same cohort as the bone publication; stiffness is not CT calcification or cardiovascular-event incidence. exposure: MK-7 180 micrograms/day evidence_span: {"source_cache": "artifacts/k2-research/25694037.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "744049d613c87cb18fd3fe9cf3d7242e3c424a8d463900701bee102d4072b8e3", "start_char": 0, "end_char": 1822, "text_sha256": "744049d613c87cb18fd3fe9cf3d7242e3c424a8d463900701bee102d4072b8e3"} [k2-p25694037] Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women. A double-blind randomised clinical trial. (2015). https://pubmed.ncbi.nlm.nih.gov/25694037/ DOI: 10.1160/th14-08-0675
Complete structured claim and evidence
MK-7 reduced dp-ucMGP versus placebo by 205.6 pmol/L in the diabetes/CVD trial.
Menaquinone-7 / MK-7 → Dephosphorylated uncarboxylated matrix Gla protein source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/31387121.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "669c0cd660524535123c231e46bba36d26e632210055aa863a3601f3c7da9621", "start_char": 0, "end_char": 2207, "text_sha256": "669c0cd660524535123c231e46bba36d26e632210055aa863a3601f3c7da9621"}
experimental_model
Six-month randomized double-blind trial
exposure
MK-7 360 micrograms/day
limitations
Small trial, 60 completed; PET activity and CT calcium mass are distinct. A nonsignificant trend is not a demonstrated increase in disease.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
68 adults with type 2 diabetes and established cardiovascular disease
plain_language
A vitamin K-related biomarker responded to treatment.
primary_references
[k2-p31387121] The effect of menaquinone-7 supplementation on vascular calcification in patients with diabetes: a randomized, double-blind, placebo-controlled trial. (2019). https://pubmed.ncbi.nlm.nih.gov/31387121/ DOI: 10.1093/ajcn/nqz147
tissue_or_cell_type
Femoral fluorine-18 NaF PET and CT
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 1176–1187
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Six-month randomized double-blind trial · source_derived_draft · unverified_draft
### k2-diabetes-marker MK-7 reduced dp-ucMGP versus placebo by 205.6 pmol/L in the diabetes/CVD trial. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A vitamin K-related biomarker responded to treatment. organism: 68 adults with type 2 diabetes and established cardiovascular disease tissue_or_cell_type: Femoral fluorine-18 NaF PET and CT experimental_model: Six-month randomized double-blind trial limitations: Small trial, 60 completed; PET activity and CT calcium mass are distinct. A nonsignificant trend is not a demonstrated increase in disease. exposure: MK-7 360 micrograms/day evidence_span: {"source_cache": "artifacts/k2-research/31387121.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "669c0cd660524535123c231e46bba36d26e632210055aa863a3601f3c7da9621", "start_char": 0, "end_char": 2207, "text_sha256": "669c0cd660524535123c231e46bba36d26e632210055aa863a3601f3c7da9621"} [k2-p31387121] The effect of menaquinone-7 supplementation on vascular calcification in patients with diabetes: a randomized, double-blind, placebo-controlled trial. (2019). https://pubmed.ncbi.nlm.nih.gov/31387121/ DOI: 10.1093/ajcn/nqz147
Complete structured claim and evidence
The between-group PET activity estimate favored an increase of 0.25 (95% CI -0.02 to 0.51; P=0.06); CT calcium-mass differences were also nonsignificant.
Menaquinone-7 / MK-7 → Femoral arterial fluorine-18 sodium fluoride PET activity source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/31387121.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "669c0cd660524535123c231e46bba36d26e632210055aa863a3601f3c7da9621", "start_char": 0, "end_char": 2207, "text_sha256": "669c0cd660524535123c231e46bba36d26e632210055aa863a3601f3c7da9621"}
experimental_model
Six-month randomized double-blind trial
exposure
MK-7 360 micrograms/day
limitations
Small trial, 60 completed; PET activity and CT calcium mass are distinct. A nonsignificant trend is not a demonstrated increase in disease.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
68 adults with type 2 diabetes and established cardiovascular disease
plain_language
This study did not show the hoped-for imaging improvement despite a better biomarker.
primary_references
[k2-p31387121] The effect of menaquinone-7 supplementation on vascular calcification in patients with diabetes: a randomized, double-blind, placebo-controlled trial. (2019). https://pubmed.ncbi.nlm.nih.gov/31387121/ DOI: 10.1093/ajcn/nqz147
tissue_or_cell_type
Femoral fluorine-18 NaF PET and CT
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 1189–1200
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Six-month randomized double-blind trial · source_derived_draft · unverified_draft
### k2-diabetes-imaging The between-group PET activity estimate favored an increase of 0.25 (95% CI -0.02 to 0.51; P=0.06); CT calcium-mass differences were also nonsignificant. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: This study did not show the hoped-for imaging improvement despite a better biomarker. organism: 68 adults with type 2 diabetes and established cardiovascular disease tissue_or_cell_type: Femoral fluorine-18 NaF PET and CT experimental_model: Six-month randomized double-blind trial limitations: Small trial, 60 completed; PET activity and CT calcium mass are distinct. A nonsignificant trend is not a demonstrated increase in disease. exposure: MK-7 360 micrograms/day evidence_span: {"source_cache": "artifacts/k2-research/31387121.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "669c0cd660524535123c231e46bba36d26e632210055aa863a3601f3c7da9621", "start_char": 0, "end_char": 2207, "text_sha256": "669c0cd660524535123c231e46bba36d26e632210055aa863a3601f3c7da9621"} [k2-p31387121] The effect of menaquinone-7 supplementation on vascular calcification in patients with diabetes: a randomized, double-blind, placebo-controlled trial. (2019). https://pubmed.ncbi.nlm.nih.gov/31387121/ DOI: 10.1093/ajcn/nqz147
Complete structured claim and evidence
MK-7 plus vitamin D did not significantly change aortic-valve calcification progression versus placebo over two years (P=0.64).
Menaquinone-7 / MK-7 → Aortic valve calcification source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/35465686.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0bd565b58d0e78923a55d154f6a341de560d5674c63989d36042543e0ddc295c", "start_char": 0, "end_char": 2233, "text_sha256": "0bd565b58d0e78923a55d154f6a341de560d5674c63989d36042543e0ddc295c"}
experimental_model
Two-year randomized double-blind AVADEC trial
exposure
MK-7 720 micrograms plus vitamin D 25 micrograms/day versus placebo
limitations
Combined intervention, valve-disease population; neither K2-only effects nor universal prevention claims follow.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
365 men, mean age 71, with aortic-valve calcium score above 300
plain_language
The combination did not slow the valve endpoint in these men.
primary_references
[k2-p35465686] Vitamin K2 and D in Patients With Aortic Valve Calcification: A Randomized Double-Blinded Clinical Trial. (2022). https://pubmed.ncbi.nlm.nih.gov/35465686/ DOI: 10.1161/circulationaha.121.057008
tissue_or_cell_type
Valve CT, echocardiography and dp-ucMGP
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 1202–1213
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two-year randomized double-blind AVADEC trial · source_derived_draft · unverified_draft
### k2-avadec-null MK-7 plus vitamin D did not significantly change aortic-valve calcification progression versus placebo over two years (P=0.64). Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The combination did not slow the valve endpoint in these men. organism: 365 men, mean age 71, with aortic-valve calcium score above 300 tissue_or_cell_type: Valve CT, echocardiography and dp-ucMGP experimental_model: Two-year randomized double-blind AVADEC trial limitations: Combined intervention, valve-disease population; neither K2-only effects nor universal prevention claims follow. exposure: MK-7 720 micrograms plus vitamin D 25 micrograms/day versus placebo evidence_span: {"source_cache": "artifacts/k2-research/35465686.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0bd565b58d0e78923a55d154f6a341de560d5674c63989d36042543e0ddc295c", "start_char": 0, "end_char": 2233, "text_sha256": "0bd565b58d0e78923a55d154f6a341de560d5674c63989d36042543e0ddc295c"} [k2-p35465686] Vitamin K2 and D in Patients With Aortic Valve Calcification: A Randomized Double-Blinded Clinical Trial. (2022). https://pubmed.ncbi.nlm.nih.gov/35465686/ DOI: 10.1161/circulationaha.121.057008
Complete structured claim and evidence
dp-ucMGP changed by -212 pmol/L with MK-7 plus vitamin D versus +45 pmol/L with placebo.
Menaquinone-7 / MK-7 → Dephosphorylated uncarboxylated matrix Gla protein source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/35465686.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0bd565b58d0e78923a55d154f6a341de560d5674c63989d36042543e0ddc295c", "start_char": 0, "end_char": 2233, "text_sha256": "0bd565b58d0e78923a55d154f6a341de560d5674c63989d36042543e0ddc295c"}
experimental_model
Two-year randomized double-blind AVADEC trial
exposure
MK-7 720 micrograms plus vitamin D 25 micrograms/day versus placebo
limitations
Combined intervention, valve-disease population; neither K2-only effects nor universal prevention claims follow.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
365 men, mean age 71, with aortic-valve calcium score above 300
plain_language
A biochemical response coexisted with a null valve-imaging result.
primary_references
[k2-p35465686] Vitamin K2 and D in Patients With Aortic Valve Calcification: A Randomized Double-Blinded Clinical Trial. (2022). https://pubmed.ncbi.nlm.nih.gov/35465686/ DOI: 10.1161/circulationaha.121.057008
tissue_or_cell_type
Valve CT, echocardiography and dp-ucMGP
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 1215–1226
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two-year randomized double-blind AVADEC trial · source_derived_draft · unverified_draft
### k2-avadec-marker dp-ucMGP changed by -212 pmol/L with MK-7 plus vitamin D versus +45 pmol/L with placebo. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A biochemical response coexisted with a null valve-imaging result. organism: 365 men, mean age 71, with aortic-valve calcium score above 300 tissue_or_cell_type: Valve CT, echocardiography and dp-ucMGP experimental_model: Two-year randomized double-blind AVADEC trial limitations: Combined intervention, valve-disease population; neither K2-only effects nor universal prevention claims follow. exposure: MK-7 720 micrograms plus vitamin D 25 micrograms/day versus placebo evidence_span: {"source_cache": "artifacts/k2-research/35465686.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0bd565b58d0e78923a55d154f6a341de560d5674c63989d36042543e0ddc295c", "start_char": 0, "end_char": 2233, "text_sha256": "0bd565b58d0e78923a55d154f6a341de560d5674c63989d36042543e0ddc295c"} [k2-p35465686] Vitamin K2 and D in Patients With Aortic Valve Calcification: A Randomized Double-Blinded Clinical Trial. (2022). https://pubmed.ncbi.nlm.nih.gov/35465686/ DOI: 10.1161/circulationaha.121.057008
Complete structured claim and evidence
Median plasma MK-7 increased from 0.50 to 6.56 micrograms/L in the active-treatment group.
Menaquinone-7 / MK-7 → Serum menaquinone-7 concentration source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/42268593.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8bd6d3cb0722f549b8a9c8f06feba3165dfd421c4ce0658b75b90a6e64e84a4b", "start_char": 0, "end_char": 2890, "text_sha256": "8bd6d3cb0722f549b8a9c8f06feba3165dfd421c4ce0658b75b90a6e64e84a4b"}
experimental_model
Two-year randomized placebo-controlled VitaK-CAC trial
exposure
MK-7 360 micrograms/day; baseline CAC 50–400
limitations
Published 2026; imaging surrogate, not demonstrated fewer infarctions, improved plaque stability or arterial calcium removal. One author disclosed grants from Gnosis and shares in Coagulation Profile outside this work.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
180 randomized symptomatic coronary-disease patients; 85 received MK-7 and 82 placebo
plain_language
The trial documented exposure as well as its imaging outcome.
primary_references
[k2-p42268593] Two Years of Menaquinone-7 Supplementation and Coronary Artery Calcification: A Randomized Clinical Trial. (2026). https://pubmed.ncbi.nlm.nih.gov/42268593/ DOI: 10.1001/jamacardio.2026.1279
tissue_or_cell_type
Coronary CT calcium score and calcium mass
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 1241–1252
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two-year randomized placebo-controlled VitaK-CAC trial · source_derived_draft · unverified_draft
### k2-vitak-exposure Median plasma MK-7 increased from 0.50 to 6.56 micrograms/L in the active-treatment group. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The trial documented exposure as well as its imaging outcome. organism: 180 randomized symptomatic coronary-disease patients; 85 received MK-7 and 82 placebo tissue_or_cell_type: Coronary CT calcium score and calcium mass experimental_model: Two-year randomized placebo-controlled VitaK-CAC trial limitations: Published 2026; imaging surrogate, not demonstrated fewer infarctions, improved plaque stability or arterial calcium removal. One author disclosed grants from Gnosis and shares in Coagulation Profile outside this work. exposure: MK-7 360 micrograms/day; baseline CAC 50–400 evidence_span: {"source_cache": "artifacts/k2-research/42268593.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8bd6d3cb0722f549b8a9c8f06feba3165dfd421c4ce0658b75b90a6e64e84a4b", "start_char": 0, "end_char": 2890, "text_sha256": "8bd6d3cb0722f549b8a9c8f06feba3165dfd421c4ce0658b75b90a6e64e84a4b"} [k2-p42268593] Two Years of Menaquinone-7 Supplementation and Coronary Artery Calcification: A Randomized Clinical Trial. (2026). https://pubmed.ncbi.nlm.nih.gov/42268593/ DOI: 10.1001/jamacardio.2026.1279
Complete structured claim and evidence
The carboxylated MGP fraction was lower in cases than controls (0.58 versus 0.69), although both absolute MGP forms were higher in cases.
Carboxylated fraction of circulating MGP → Calciphylaxis source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/k2-research/28049648.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e00861b3fa66dc1bd0b5041cd289397c5658586b0656330c6bd77d0097ddd092", "start_char": 0, "end_char": 1485, "text_sha256": "e00861b3fa66dc1bd0b5041cd289397c5658586b0656330c6bd77d0097ddd092"}
experimental_model
Matched case-control study
exposure
Matching included warfarin use; vitamin K deficiency associations
limitations
Observational association; neither causation nor treatment efficacy is established.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
20 hemodialysis calciphylaxis cases and 20 controls
plain_language
Total protein and the fraction correctly modified are different measurements.
primary_references
[k2-p28049648] Vitamin K-Dependent Carboxylation of Matrix Gla Protein Influences the Risk of Calciphylaxis. (2017). https://pubmed.ncbi.nlm.nih.gov/28049648/ DOI: 10.1681/asn.2016060651
tissue_or_cell_type
Circulating MGP carboxylation
trigger_kind
biomarker_context Imported condition classification; unverified.
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 1254–1265
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Matched case-control study · source_derived_draft · unverified_draft
### k2-calciphylaxis-marker The carboxylated MGP fraction was lower in cases than controls (0.58 versus 0.69), although both absolute MGP forms were higher in cases. Condition category: biomarker_context nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Total protein and the fraction correctly modified are different measurements. organism: 20 hemodialysis calciphylaxis cases and 20 controls tissue_or_cell_type: Circulating MGP carboxylation experimental_model: Matched case-control study limitations: Observational association; neither causation nor treatment efficacy is established. exposure: Matching included warfarin use; vitamin K deficiency associations evidence_span: {"source_cache": "artifacts/k2-research/28049648.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e00861b3fa66dc1bd0b5041cd289397c5658586b0656330c6bd77d0097ddd092", "start_char": 0, "end_char": 1485, "text_sha256": "e00861b3fa66dc1bd0b5041cd289397c5658586b0656330c6bd77d0097ddd092"} [k2-p28049648] Vitamin K-Dependent Carboxylation of Matrix Gla Protein Influences the Risk of Calciphylaxis. (2017). https://pubmed.ncbi.nlm.nih.gov/28049648/ DOI: 10.1681/asn.2016060651
Complete structured claim and evidence
A concentrated vitamin K-dependent carboxylase preparation converted glutamate residues of decarboxylated bovine osteocalcin into gamma-carboxyglutamate in vitro.
Gamma-glutamyl carboxylase / GGCX → Decarboxylated osteocalcin source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Vitamin D regulates osteocalcin expression in specified models; vitamin K-dependent carboxylation modifies its protein product through a distinct enzyme reaction.
evidence_locator
Abstract: reported experimental results
evidence_scope
D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison.
experimental_model
Microsomal vitamin K-dependent carboxylase enriched about 100-fold; bovine osteocalcin substrate and CO2-incorporation assay
exposure
50 mM bicarbonate, excess enriched carboxylase and limiting decarboxylated osteocalcin; vitamin K-dependent reaction conditions.
limitations
In-vitro modification of a defined substrate; no D-plus-K supplementation regimen, K2-specific necessity, improved fracture outcome or obligatory supplement pairing was tested.
nutrient
Vitamin D2 and D3 · Vitamin D2 and D3
nutrient_topic
Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3
organism
Bos taurus osteocalcin; liver-derived enzyme preparation
plain_language
Osteocalcin needs a separate vitamin K-dependent protein-modification step; making more osteocalcin is not the same reaction.
primary_references
[vdm-soute1987] Vitamin K-dependent carboxylase: increased efficiency of the carboxylation reaction. (1987). https://pubmed.ncbi.nlm.nih.gov/3495900/ DOI: 10.1055/s-0038-1651066
tissue_or_cell_type
Cell-free enzyme assay
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 889–903
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Microsomal vitamin K-dependent carboxylase enriched about 100-fold; bovine osteocalcin substrate and CO2-incorporation assay · source_derived_draft · unverified_draft
### vdm-vitamin-k-carboxylase-modifies-osteocalcin A concentrated vitamin K-dependent carboxylase preparation converted glutamate residues of decarboxylated bovine osteocalcin into gamma-carboxyglutamate in vitro. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Osteocalcin needs a separate vitamin K-dependent protein-modification step; making more osteocalcin is not the same reaction. organism: Bos taurus osteocalcin; liver-derived enzyme preparation tissue_or_cell_type: Cell-free enzyme assay experimental_model: Microsomal vitamin K-dependent carboxylase enriched about 100-fold; bovine osteocalcin substrate and CO2-incorporation assay limitations: In-vitro modification of a defined substrate; no D-plus-K supplementation regimen, K2-specific necessity, improved fracture outcome or obligatory supplement pairing was tested. exposure: 50 mM bicarbonate, excess enriched carboxylase and limiting decarboxylated osteocalcin; vitamin K-dependent reaction conditions. cross_nutrient: Vitamin D regulates osteocalcin expression in specified models; vitamin K-dependent carboxylation modifies its protein product through a distinct enzyme reaction. evidence_locator: Abstract: reported experimental results nutrient: Vitamin D2 and D3 evidence_scope: D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison. [vdm-soute1987] Vitamin K-dependent carboxylase: increased efficiency of the carboxylation reaction. (1987). https://pubmed.ncbi.nlm.nih.gov/3495900/ DOI: 10.1055/s-0038-1651066
Complete structured claim and evidence
Calcitriol increased human osteocalcin mRNA about 1.8-fold in calvaria of mice carrying the human osteocalcin genomic transgene.
Calcitriol → Human BGLAP mRNA source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Vitamin D–vitamin K boundary: vitamin D-regulated osteocalcin expression is distinct from subsequent vitamin K-dependent carboxylation.
evidence_locator
Abstract: reported experimental results
evidence_scope
D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison.
experimental_model
Human osteocalcin genomic transgene in mice; calvarial mRNA analysis
exposure
Repeated calcitriol administration; exact dose and calvarial mRNA collection time not specified in the retrieved abstract.
limitations
Human transgene in mouse tissue is not a human supplementation trial. Transcript induction does not measure vitamin K-dependent carboxylation.
nutrient
Vitamin D2 and D3 · Vitamin D2 and D3
nutrient_topic
Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3
organism
Mus musculus with human BGLAP transgene
plain_language
The human osteocalcin gene responded to active vitamin D in this engineered mouse model.
primary_references
[vdm-zhang1997] Analysis of osteocalcin expression in transgenic mice reveals a species difference in vitamin D regulation of mouse and human osteocalcin genes. (1997). https://pubmed.ncbi.nlm.nih.gov/9333117/ DOI: 10.1359/jbmr.1997.12.10.1570
tissue_or_cell_type
Calvaria
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 857–871
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human osteocalcin genomic transgene in mice; calvarial mRNA analysis · source_derived_draft · unverified_draft
### vdm-calcitriol-induces-human-osteocalcin-transgene Calcitriol increased human osteocalcin mRNA about 1.8-fold in calvaria of mice carrying the human osteocalcin genomic transgene. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The human osteocalcin gene responded to active vitamin D in this engineered mouse model. organism: Mus musculus with human BGLAP transgene tissue_or_cell_type: Calvaria experimental_model: Human osteocalcin genomic transgene in mice; calvarial mRNA analysis limitations: Human transgene in mouse tissue is not a human supplementation trial. Transcript induction does not measure vitamin K-dependent carboxylation. exposure: Repeated calcitriol administration; exact dose and calvarial mRNA collection time not specified in the retrieved abstract. cross_nutrient: Vitamin D–vitamin K boundary: vitamin D-regulated osteocalcin expression is distinct from subsequent vitamin K-dependent carboxylation. evidence_locator: Abstract: reported experimental results nutrient: Vitamin D2 and D3 evidence_scope: D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison. [vdm-zhang1997] Analysis of osteocalcin expression in transgenic mice reveals a species difference in vitamin D regulation of mouse and human osteocalcin genes. (1997). https://pubmed.ncbi.nlm.nih.gov/9333117/ DOI: 10.1359/jbmr.1997.12.10.1570
Complete structured claim and evidence
In primary calvarial osteoblast cultures from the same transgenic mice, calcitriol inhibited endogenous mouse osteocalcin accumulation while increasing human osteocalcin production.
Calcitriol → Osteocalcin / BGLAP source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Vitamin D–vitamin K boundary: gene expression and carboxylation are distinct, and osteocalcin transcription is species-dependent.
evidence_locator
Abstract: reported experimental results
evidence_scope
D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison.
experimental_model
Primary calvarial osteoblasts from human-osteocalcin-transgenic mice; species-specific protein assays
exposure
Calcitriol exposure of primary cultures; exact culture dose/time not given in the retrieved abstract.
limitations
Species and gene-regulatory context explain the difference; this is not an orange scientific conflict and does not predict human fracture outcomes.
nutrient
Vitamin D2 and D3 · Vitamin D2 and D3
nutrient_topic
Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3
organism
Mus musculus with human BGLAP transgene
plain_language
Mouse and human osteocalcin genes responded differently in the same experimental setting.
primary_references
[vdm-zhang1997] Analysis of osteocalcin expression in transgenic mice reveals a species difference in vitamin D regulation of mouse and human osteocalcin genes. (1997). https://pubmed.ncbi.nlm.nih.gov/9333117/ DOI: 10.1359/jbmr.1997.12.10.1570
tissue_or_cell_type
Calvarial osteoblast culture
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 873–887
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Primary calvarial osteoblasts from human-osteocalcin-transgenic mice; species-specific protein assays · source_derived_draft · unverified_draft
### vdm-calcitriol-mouse-osteocalcin-culture-scope In primary calvarial osteoblast cultures from the same transgenic mice, calcitriol inhibited endogenous mouse osteocalcin accumulation while increasing human osteocalcin production. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Mouse and human osteocalcin genes responded differently in the same experimental setting. organism: Mus musculus with human BGLAP transgene tissue_or_cell_type: Calvarial osteoblast culture experimental_model: Primary calvarial osteoblasts from human-osteocalcin-transgenic mice; species-specific protein assays limitations: Species and gene-regulatory context explain the difference; this is not an orange scientific conflict and does not predict human fracture outcomes. exposure: Calcitriol exposure of primary cultures; exact culture dose/time not given in the retrieved abstract. cross_nutrient: Vitamin D–vitamin K boundary: gene expression and carboxylation are distinct, and osteocalcin transcription is species-dependent. evidence_locator: Abstract: reported experimental results nutrient: Vitamin D2 and D3 evidence_scope: D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison. [vdm-zhang1997] Analysis of osteocalcin expression in transgenic mice reveals a species difference in vitamin D regulation of mouse and human osteocalcin genes. (1997). https://pubmed.ncbi.nlm.nih.gov/9333117/ DOI: 10.1359/jbmr.1997.12.10.1570
Complete structured claim and evidence
Recombinant human CYP4F2 catalyzed terminal side-chain hydroxylation of alpha-tocopherol to its 13′-hydroxy product.
Human cytochrome P450 4F2 → 13′-Hydroxy-alpha-tocopherol source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Recombinant human P450 enzyme comparison
exposure
alpha-Tocopherol substrate with NADPH; quantitative incubation details not assigned here.
limitations
Initial oxidation only; other enzymes perform subsequent side-chain shortening.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Human protein in recombinant microsomes
plain_language
CYP4F2 begins breakdown of this tocopherol form.
primary_references
[sontag2002] Cytochrome P450 omega-hydroxylase pathway of tocopherol catabolism. Novel mechanism of regulation of vitamin E status. (2002). https://pubmed.ncbi.nlm.nih.gov/11997390/ DOI: 10.1074/jbc.m201466200
tissue_or_cell_type
Microsomal enzyme preparation
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 402–413
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human P450 enzyme comparison · source_derived_draft · unverified_draft
### ve-transport-cyp4f2-alpha-hydroxylation Recombinant human CYP4F2 catalyzed terminal side-chain hydroxylation of alpha-tocopherol to its 13′-hydroxy product. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: CYP4F2 begins breakdown of this tocopherol form. organism: Human protein in recombinant microsomes tissue_or_cell_type: Microsomal enzyme preparation experimental_model: Recombinant human P450 enzyme comparison limitations: Initial oxidation only; other enzymes perform subsequent side-chain shortening. exposure: alpha-Tocopherol substrate with NADPH; quantitative incubation details not assigned here. cross_nutrient: false [sontag2002] Cytochrome P450 omega-hydroxylase pathway of tocopherol catabolism. Novel mechanism of regulation of vitamin E status. (2002). https://pubmed.ncbi.nlm.nih.gov/11997390/ DOI: 10.1074/jbc.m201466200
Complete structured claim and evidence
Recombinant human CYP4F2 catalyzed terminal side-chain hydroxylation of gamma-tocopherol to its 13′-hydroxy product.
Human cytochrome P450 4F2 → 13′-Hydroxy-gamma-tocopherol source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Recombinant human P450 enzyme comparison
exposure
gamma-Tocopherol substrate with NADPH; quantitative incubation details not assigned here.
limitations
Initial oxidation only; other enzymes perform subsequent side-chain shortening.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Human protein in recombinant microsomes
plain_language
CYP4F2 begins breakdown of this tocopherol form.
primary_references
[sontag2002] Cytochrome P450 omega-hydroxylase pathway of tocopherol catabolism. Novel mechanism of regulation of vitamin E status. (2002). https://pubmed.ncbi.nlm.nih.gov/11997390/ DOI: 10.1074/jbc.m201466200
tissue_or_cell_type
Microsomal enzyme preparation
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 415–426
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human P450 enzyme comparison · source_derived_draft · unverified_draft
### ve-transport-cyp4f2-gamma-hydroxylation Recombinant human CYP4F2 catalyzed terminal side-chain hydroxylation of gamma-tocopherol to its 13′-hydroxy product. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: CYP4F2 begins breakdown of this tocopherol form. organism: Human protein in recombinant microsomes tissue_or_cell_type: Microsomal enzyme preparation experimental_model: Recombinant human P450 enzyme comparison limitations: Initial oxidation only; other enzymes perform subsequent side-chain shortening. exposure: gamma-Tocopherol substrate with NADPH; quantitative incubation details not assigned here. cross_nutrient: false [sontag2002] Cytochrome P450 omega-hydroxylase pathway of tocopherol catabolism. Novel mechanism of regulation of vitamin E status. (2002). https://pubmed.ncbi.nlm.nih.gov/11997390/ DOI: 10.1074/jbc.m201466200
Complete structured claim and evidence
Human CYP4F2-expressing microsomes hydroxylated phylloquinone, demonstrating substrate overlap with tocopherol catabolism.
Human cytochrome P450 4F2 → Omega-hydroxyphylloquinone source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Recombinant CYP4F2 kinetic assay
exposure
25 pmol CYP4F2; labeled phylloquinone 1–100 µM; 1 mM NADPH; 30 min at 37 °C.
limitations
Shared substrate use alone does not imply vitamin E accelerates vitamin K depletion.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Human protein in insect microsomes
plain_language
Vitamins E and K1 share an initial catabolic enzyme.
primary_references
[farley2013] ω-Hydroxylation of phylloquinone by CYP4F2 is not increased by α-tocopherol. (2013). https://pubmed.ncbi.nlm.nih.gov/23650179/ DOI: 10.1002/mnfr.201200797
tissue_or_cell_type
Microsomal enzyme preparation
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 454–465
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant CYP4F2 kinetic assay · source_derived_draft · unverified_draft
### ve-transport-cyp4f2-k1-hydroxylation Human CYP4F2-expressing microsomes hydroxylated phylloquinone, demonstrating substrate overlap with tocopherol catabolism. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamins E and K1 share an initial catabolic enzyme. organism: Human protein in insect microsomes tissue_or_cell_type: Microsomal enzyme preparation experimental_model: Recombinant CYP4F2 kinetic assay limitations: Shared substrate use alone does not imply vitamin E accelerates vitamin K depletion. exposure: 25 pmol CYP4F2; labeled phylloquinone 1–100 µM; 1 mM NADPH; 30 min at 37 °C. cross_nutrient: true [farley2013] ω-Hydroxylation of phylloquinone by CYP4F2 is not increased by α-tocopherol. (2013). https://pubmed.ncbi.nlm.nih.gov/23650179/ DOI: 10.1002/mnfr.201200797
Complete structured claim and evidence
Alpha-tocopherol did not increase phylloquinone omega-hydroxylation in CYP4F2 microsomes; the study reported a slight decrease in apparent phylloquinone Vmax.
RRR-alpha-tocopherol → CYP4F2-mediated phylloquinone omega-hydroxylation source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Recombinant human CYP4F2 co-substrate kinetics
exposure
Labeled phylloquinone 0–50 µM with RRR-alpha-tocopherol 0–50 µM or SRR-alpha-tocopherol 0–100 µM; 30 min, 37 °C, 1 mM NADPH.
limitations
Does not exclude other mechanisms of vitamin E–K interaction in animals or humans.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Human protein in insect microsomes
plain_language
This assay did not support faster vitamin K1 breakdown caused by alpha-tocopherol.
primary_references
[farley2013] ω-Hydroxylation of phylloquinone by CYP4F2 is not increased by α-tocopherol. (2013). https://pubmed.ncbi.nlm.nih.gov/23650179/ DOI: 10.1002/mnfr.201200797
tissue_or_cell_type
Microsomal enzyme preparation
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 467–478
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human CYP4F2 co-substrate kinetics · source_derived_draft · unverified_draft
### ve-transport-alpha-does-not-activate-k1-catabolism Alpha-tocopherol did not increase phylloquinone omega-hydroxylation in CYP4F2 microsomes; the study reported a slight decrease in apparent phylloquinone Vmax. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: This assay did not support faster vitamin K1 breakdown caused by alpha-tocopherol. organism: Human protein in insect microsomes tissue_or_cell_type: Microsomal enzyme preparation experimental_model: Recombinant human CYP4F2 co-substrate kinetics limitations: Does not exclude other mechanisms of vitamin E–K interaction in animals or humans. exposure: Labeled phylloquinone 0–50 µM with RRR-alpha-tocopherol 0–50 µM or SRR-alpha-tocopherol 0–100 µM; 30 min, 37 °C, 1 mM NADPH. cross_nutrient: true [farley2013] ω-Hydroxylation of phylloquinone by CYP4F2 is not increased by α-tocopherol. (2013). https://pubmed.ncbi.nlm.nih.gov/23650179/ DOI: 10.1002/mnfr.201200797
Complete structured claim and evidence
High-dose RRR-alpha-tocopherol increased PIVKA-II in both 12-week adult trials: mean values rose from 1.7 to 11.9 ng/mL and from 1.8 to 5.3 ng/mL.
RRR-alpha-tocopherol → Undercarboxylated prothrombin / PIVKA-II source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Two independent 12-week randomized trials; 38 adults with rheumatoid arthritis and 32 healthy men
exposure
RRR-alpha-tocopherol 1000 IU/day; participants were not receiving oral anticoagulant therapy.
limitations
Biochemical marker study, not a bleeding-events trial. The study does not identify CYP4F2 activation, direct GGCX inhibition or clinical vitamin K deficiency as the causal route.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
High-dose vitamin E altered a vitamin K-dependent clotting-protein marker.
primary_references
[e-clin-booth2004] Effect of vitamin E supplementation on vitamin K status in adults with normal coagulation status. (2004). https://pubmed.ncbi.nlm.nih.gov/15213041/ DOI: 10.1093/ajcn/80.1.143
tissue_or_cell_type
Circulation and vitamin K-dependent carboxylation
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 1258–1269
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two independent 12-week randomized trials; 38 adults with rheumatoid arthritis and 32 healthy men · source_derived_draft · unverified_draft
### e-clin-vitamin-k-pivka High-dose RRR-alpha-tocopherol increased PIVKA-II in both 12-week adult trials: mean values rose from 1.7 to 11.9 ng/mL and from 1.8 to 5.3 ng/mL. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: High-dose vitamin E altered a vitamin K-dependent clotting-protein marker. organism: Homo sapiens tissue_or_cell_type: Circulation and vitamin K-dependent carboxylation experimental_model: Two independent 12-week randomized trials; 38 adults with rheumatoid arthritis and 32 healthy men limitations: Biochemical marker study, not a bleeding-events trial. The study does not identify CYP4F2 activation, direct GGCX inhibition or clinical vitamin K deficiency as the causal route. exposure: RRR-alpha-tocopherol 1000 IU/day; participants were not receiving oral anticoagulant therapy. cross_nutrient: true [e-clin-booth2004] Effect of vitamin E supplementation on vitamin K status in adults with normal coagulation status. (2004). https://pubmed.ncbi.nlm.nih.gov/15213041/ DOI: 10.1093/ajcn/80.1.143
Complete structured claim and evidence
Plasma phylloquinone and percentage undercarboxylated osteocalcin did not change significantly with vitamin E supplementation despite increased PIVKA-II.
RRR-alpha-tocopherol → Undercarboxylated osteocalcin source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Two independent 12-week randomized trials; 38 adults with rheumatoid arthritis and 32 healthy men
exposure
RRR-alpha-tocopherol 1000 IU/day; participants were not receiving oral anticoagulant therapy.
limitations
Biochemical marker study, not a bleeding-events trial. The study does not identify CYP4F2 activation, direct GGCX inhibition or clinical vitamin K deficiency as the causal route.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Homo sapiens
plain_language
The vitamin K-related markers did not all respond in the same way.
primary_references
[e-clin-booth2004] Effect of vitamin E supplementation on vitamin K status in adults with normal coagulation status. (2004). https://pubmed.ncbi.nlm.nih.gov/15213041/ DOI: 10.1093/ajcn/80.1.143
tissue_or_cell_type
Circulation and vitamin K-dependent carboxylation
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 1271–1282
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two independent 12-week randomized trials; 38 adults with rheumatoid arthritis and 32 healthy men · source_derived_draft · unverified_draft
### e-clin-vitamin-k-marker-boundary Plasma phylloquinone and percentage undercarboxylated osteocalcin did not change significantly with vitamin E supplementation despite increased PIVKA-II. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: The vitamin K-related markers did not all respond in the same way. organism: Homo sapiens tissue_or_cell_type: Circulation and vitamin K-dependent carboxylation experimental_model: Two independent 12-week randomized trials; 38 adults with rheumatoid arthritis and 32 healthy men limitations: Biochemical marker study, not a bleeding-events trial. The study does not identify CYP4F2 activation, direct GGCX inhibition or clinical vitamin K deficiency as the causal route. exposure: RRR-alpha-tocopherol 1000 IU/day; participants were not receiving oral anticoagulant therapy. cross_nutrient: true [e-clin-booth2004] Effect of vitamin E supplementation on vitamin K status in adults with normal coagulation status. (2004). https://pubmed.ncbi.nlm.nih.gov/15213041/ DOI: 10.1093/ajcn/80.1.143
Complete structured claim and evidence
Vitamin K1 hydroquinone reacted with alpha-tocopheroxyl in stopped-flow assays; it regenerated vitamin E more rapidly than ubiquinol-10 across the tested ethanol, benzene and isopropanol/water solvent systems.
Phylloquinol / vitamin K1 hydroquinone → Alpha-tocopherol source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_location
Primary abstract
experimental_model
Biological hydroquinone comparison
exposure
Reduced K1; isopropanol/water 5:1 v/v and separate organic solvents.
limitations
Does not establish dietary K/E synergy, clinical benefit or competition in coagulation.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Cell-free
plain_language
The reduced form of vitamin K1 recycled vitamin E in solution.
primary_references
[ver-mukai1992] Stopped-flow kinetic study of vitamin E regeneration reaction with biological hydroquinones (reduced forms of ubiquinone, vitamin K, and tocopherolquinone) in solution. (1992). https://pubmed.ncbi.nlm.nih.gov/1429580/ DOI: 10.1016/s0021-9258(18)41666-3
tissue_or_cell_type
Chemical solutions
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 536–548
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Biological hydroquinone comparison · source_derived_draft · unverified_draft
### ver-phylloquinol-regeneration Vitamin K1 hydroquinone reacted with alpha-tocopheroxyl in stopped-flow assays; it regenerated vitamin E more rapidly than ubiquinol-10 across the tested ethanol, benzene and isopropanol/water solvent systems. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: The reduced form of vitamin K1 recycled vitamin E in solution. organism: Cell-free tissue_or_cell_type: Chemical solutions experimental_model: Biological hydroquinone comparison limitations: Does not establish dietary K/E synergy, clinical benefit or competition in coagulation. exposure: Reduced K1; isopropanol/water 5:1 v/v and separate organic solvents. cross_nutrient: true evidence_location: Primary abstract [ver-mukai1992] Stopped-flow kinetic study of vitamin E regeneration reaction with biological hydroquinones (reduced forms of ubiquinone, vitamin K, and tocopherolquinone) in solution. (1992). https://pubmed.ncbi.nlm.nih.gov/1429580/ DOI: 10.1016/s0021-9258(18)41666-3
Complete structured claim and evidence
FSP1 can regenerate reduced CoQ as a parallel, glutathione-independent defense alongside GPX4.
FSP1 → Reduced CoQ10 source_derived_draftsource_reported: Cell/biochemical and animal cancer models; supplied-source synthesis with a narrow FSP1 primary-study spot check.
Experimental context and source evidence
availability_state
Selenium restriction becomes severe enough to compromise GPX4 function in a susceptible context.
experimental_scope
Cell and cancer-model evidence for parallel defenses; GPX4 may be relatively preserved during nutritional restriction.
limitations
The source does not establish a nutritional dose or plasma value that disables GPX4. GPX4 deletion or drug inhibition is not equivalent to ordinary dietary deficiency; parallel protection is not guaranteed in every cell.
trigger_kind
nutrient_deficiency
Selenium deficiency: a mechanism-first reference · lines 123–123
Supplied selenium deficiency reference · supports · Supplied reference; verify the primary study and experimental context. · source_derived_draft · unverified_draft
But GPX4 is not the only barrier between a cell and ferroptosis. The FSP1–CoQ10 system provides a parallel, glutathione-independent defense by regenerating reduced CoQ, which can trap lipid radicals. Other systems also contribute. Evidence: cell and cancer-model experiments. [8,9]
Complete structured claim and evidence
At a physiological vitamin E-to-phospholipid ratio, inhibition of iron-dependent lipid peroxidation in rat liver microsomes and dispersed microsomal lipids was observed only when PHGPX (GPX4) and glutathione were also present.
Alpha-tocopherol → Lipid peroxidation source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_location
Primary abstract
experimental_model
Microsomes and Triton-dispersed lipid micelles
exposure
Iron-dependent peroxidation; physiological vitamin E:phospholipid ratio as reported in abstract.
limitations
Exact concentrations are not available in the inspected abstract. Model-specific dependence does not imply every membrane requires added GPX4 to show E protection.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Rattus norvegicus
plain_language
Vitamin E protection depended on peroxide removal by the GPX4/glutathione system in these preparations.
primary_references
[ver-maiorino1989] Microsomal lipid peroxidation: effect of vitamin E and its functional interaction with phospholipid hydroperoxide glutathione peroxidase. (1989). https://pubmed.ncbi.nlm.nih.gov/2586229/ DOI: 10.1007/bf02535211
tissue_or_cell_type
Liver microsomal lipids
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 592–604
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Microsomes and Triton-dispersed lipid micelles · source_derived_draft · unverified_draft
### ver-gpx4-gsh-tocopherol-cooperation At a physiological vitamin E-to-phospholipid ratio, inhibition of iron-dependent lipid peroxidation in rat liver microsomes and dispersed microsomal lipids was observed only when PHGPX (GPX4) and glutathione were also present. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin E protection depended on peroxide removal by the GPX4/glutathione system in these preparations. organism: Rattus norvegicus tissue_or_cell_type: Liver microsomal lipids experimental_model: Microsomes and Triton-dispersed lipid micelles limitations: Exact concentrations are not available in the inspected abstract. Model-specific dependence does not imply every membrane requires added GPX4 to show E protection. exposure: Iron-dependent peroxidation; physiological vitamin E:phospholipid ratio as reported in abstract. cross_nutrient: true evidence_location: Primary abstract [ver-maiorino1989] Microsomal lipid peroxidation: effect of vitamin E and its functional interaction with phospholipid hydroperoxide glutathione peroxidase. (1989). https://pubmed.ncbi.nlm.nih.gov/2586229/ DOI: 10.1007/bf02535211
Complete structured claim and evidence

Availability and dependencies

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

MK-4 supply can fall when its biosynthetic enzyme is impaired

Condition: machinery_impairment · UBIAD1 knockdown

Normal role: UBIAD1 converts precursor vitamin K molecules into MK-4.

Recorded consequence: Reduced conversion of labeled precursors into MK-4.

Scope: Human-cell biosynthesis experiment

Different defects in the same protein need not produce the same shortage

Condition: machinery_impairment · Defined UBIAD1 variants

Normal role: UBIAD1 supplies MK-4 for vitamin K-dependent carboxylation.

Recorded consequence: Variant-dependent loss of synthesis and reporter carboxylation.

Scope: Human reporter-cell model

Removing a calcification-control protein damages arteries and cartilage

Condition: machinery_impairment · Mgp deletion

Normal role: MGP helps inhibit inappropriate extracellular mineral deposition.

Recorded consequence: Arterial and cartilage calcification, vascular rupture and skeletal abnormalities.

Scope: Mgp-null mice

Bone strength depends on organization as well as mineral quantity

Condition: machinery_impairment · Deletion of Bglap and Bglap2

Normal role: Osteocalcin contributes to alignment of mineral crystals relative to collagen.

Recorded consequence: Disorganized apatite alignment and lower strength without the claimed change in bone quantity.

Scope: Mouse osteocalcin knockout

Recycling inhibition can leave a calcification-control protein undercarboxylated

Condition: machinery_impairment · Warfarin exposure with elevated calcium

Normal role: Vitamin K supports MGP carboxylation.

Recorded consequence: More uncarboxylated MGP and calcium salt deposition.

Scope: Human vascular-cell model; pharmacological exposure

Binding a receptor does not guarantee activating it

Condition: machinery_impairment · Carboxylation inhibition or relevant domain mutations

Normal role: Carboxylated GAS6 bridges phosphatidylserine-bearing surfaces and TAM receptors.

Recorded consequence: Loss of signaling despite retained receptor binding by some variants.

Scope: GAS6/TAM reporter-cell experiments

Vitamin K-dependent bone signaling can also support bone resorption

Condition: machinery_impairment · Osteoblast-specific Ggcx deletion

Normal role: Osteoblast carboxylation supports signals to osteoclast precursors.

Recorded consequence: Fewer multinucleated osteoclasts and increased bone mass.

Scope: Six-month-old male knockout mice

K2 antioxidant protection depends on its recycling machinery

Condition: machinery_impairment · FSP1 loss or inhibition

Normal role: FSP1 regenerates reduced vitamin K for membrane radical trapping.

Recorded consequence: Weaker protection by MK-4 and K1 in the ferroptosis assays.

Scope: Engineered mammalian cells

Vitamin K2 rescued an experimental fly mitochondrial defect

Condition: machinery_impairment · Heix/Pink1-associated mitochondrial dysfunction

Normal role: Heix supports the vitamin K2-related pathway in flies.

Recorded consequence: K2 restored mitochondrial function and ATP production in the model.

Scope: Drosophila genetic experiments

MK-4 did not replace missing CoQ in human-cell respiration

Condition: machinery_impairment · CoQ biosynthetic deficiency

Normal role: CoQ supports mitochondrial electron transfer.

Recorded consequence: MK-4 entered mitochondria but did not restore respiratory electron flow or ATP synthesis.

Scope: Human deficient-cell and yeast experiments

A recycling defect can impair vitamin K-dependent clotting proteins

Condition: machinery_impairment · Pathogenic VKORC1 variation

Normal role: VKORC1 recycles the vitamin K cofactor.

Recorded consequence: Combined coagulation-factor deficiency or variant-specific anticoagulant resistance.

Scope: Human genetics and expression experiments

Severe failure of recycling can cause bleeding

Condition: machinery_impairment · Vkorc1 deletion

Normal role: VKORC1 supports maturation of carboxylated clotting factors.

Recorded consequence: Severe factor deficiency and predominantly intracerebral hemorrhage.

Scope: Postnatal knockout mice

Supplying vitamin K may only partly compensate for a damaged modifying enzyme

Condition: machinery_impairment · Compound-heterozygous GGCX mutations

Normal role: GGCX modifies several coagulation and anticoagulant proteins.

Recorded consequence: Combined factor deficiency with only partial correction by vitamin K.

Scope: Human inherited bleeding-disorder case

Low vitamin K supply affects proteins unequally

Condition: nutrient_deficiency · Controlled phylloquinone restriction

Normal role: Vitamin K supports prothrombin and osteocalcin carboxylation.

Recorded consequence: Lower carboxylation with different responses during repletion.

Scope: Older women in a metabolic-unit study; K1 intervention, shared pathway

A small MK-7 dose can alter vitamin K-antagonist anticoagulation

Condition: machinery_impairment · MK-7 added to established acenocoumarol dosing

Normal role: Vitamin K supply influences carboxylation during VKA treatment.

Recorded consequence: Lower INR and increased thrombin generation in susceptible participants.

Scope: Controlled healthy-volunteer anticoagulation study

A low carboxylated fraction is a marker, not proof of a treatment effect

Condition: biomarker_context · Calciphylaxis in dialysis

Normal role: MGP carboxylation contributes to calcification control.

Recorded consequence: Lower relative carboxylated MGP despite higher absolute carboxylated and uncarboxylated MGP levels.

Scope: Matched human case-control study

The sources

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

Selenium deficiency: a mechanism-first referenceSupplied selenium deficiency reference · unverified_draftRead preserved source
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source

Recorded disagreements

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

Open questions in this collection

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

How do serum exposure, tissue conversion and individual menaquinone forms predict clinical outcomes?Longer serum persistence is not a direct measure of bone delivery, clinical superiority or an equivalent MK-4/MK-7 dose.
Which K2 regimens, if any, reduce fractures or cardiovascular events in each clinical population?Protein markers, BMD, stiffness and CT progression are different endpoints; dose, population, cointerventions and follow-up differ across these trials.
What defines a clinically validated isolated K2 deficiency independently of K1 and the shared vitamin K cycle?Undercarboxylated proteins indicate pathway status but do not uniquely identify which dietary vitamer is lacking.
When do magnesium, NAD(P)H or other shared cofactors limit vitamin K functions in people?Enzyme and redox dependencies are not proof that extra mineral or B-vitamin supplements improve outcomes when status is already adequate.
How much usable K2 does the human gut microbiome deliver to each tissue?Bacterial menaquinone production alone does not quantify host absorption or establish adequate supply; the chapter does not infer that antibiotics automatically cause isolated K2 deficiency.

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

Evidence, AI assistance and curation standards

Vitamin K2 / menaquinone family

The mechanisms

GGCX couples oxidation of reduced vitamin K to conversion of protein-bound glutamate into gamma-carboxyglutamate.

Silencing the identified VKORC1 gene reduced vitamin K epoxide reductase activity; recombinant expression restored warfarin-sensitive enzyme activity.

Human UBIAD1 expression supported conversion of labeled vitamin K precursors to MK-4, identified by deuterium NMR.

MK-7 showed more stable serum levels and seven- to eightfold higher accumulation during repeated intake than K1 in the comparison.

Full-length MGP and its gamma-carboxylated domain inhibited calcium deposition in the tested vascular-cell model.

Deleting Bglap and Bglap2 disrupted apatite-crystal orientation relative to collagen while collagen orientation and crystal size remained normal.

Recombinant carboxylated GAS6 increased precursor fusion, osteoclast size and nuclei per osteoclast in culture.

FSP1 reduced vitamin K quinones to radical-trapping hydroquinones using NAD(P)H.

Dietary K1 restriction reduced prothrombin and osteocalcin gamma-carboxylation and lowered plasma K1 and urinary Gla excretion.

MK-7 at 45 micrograms/day lowered mean INR and uncarboxylated factor II by about 40%; lower doses altered anticoagulation in some participants.

After three years, BMD declined without significant between-group differences, and microarchitecture and turnover changes were also similar.

Median CAC rose from 135 to 184 with MK-7 and from 145 to 214 with placebo over two years; adjusted group trajectories differed (P=0.02).

UBIAD1-targeted siRNA inhibited labeled MK-4 formation in human cells.

Warfarin did not inhibit UBIAD1-mediated MK-4 biosynthesis in the reported experiments.

Rat tracer experiments identified menadione derived from oral phylloquinone as a circulating precursor of tissue MK-4.

Product analysis identified reduced menadione, rather than its quinone form, as an intermediate in UBIAD1-mediated MK-4 formation.

UBIAD1 synthesized MK-4 using GGPP as the isoprenyl side-chain source.

Mutational analysis assigned conserved domain IV to magnesium/isoprenyl-side-chain interactions.

High added magnesium inhibited MK-4 synthesis with GGPP in the microsomal assay; residual microsomal magnesium prevented a zero-magnesium conclusion.

UBIAD1 N102S retained about 82% of MK-4 biosynthetic activity and did not impair reporter carboxylation.

UBIAD1 G186R significantly impaired both MK-4 biosynthesis and vitamin K-dependent reporter carboxylation.

Serum MK-7 peaked six hours after the single dose, remained detectable to 48 hours, and rose during seven-day dosing.

MK-4 was not detected in serum after the tested 420-microgram dose and serum MK-4 did not increase with the seven-day 60-microgram regimen.

MK-7 produced more complete osteocalcin carboxylation than the compared K1 regimen.

Purified CYP4F2 catalyzed MK-4 terminal side-chain hydroxylation in vitro.

Purified CYP4F11 catalyzed MK-4 terminal side-chain hydroxylation in vitro.

CYP4F2, but not CYP4F11, supported sequential MK-4 oxidation to the omega-acid without apparent release of the aldehyde intermediate.

Microsomal NAD-dependent alcohol and aldehyde dehydrogenase activities converted the MK-4 omega-alcohol to its acid.

Vitamin K-dependent protein propeptide binding stabilized GGCX transmembrane helices 6 and 7 and created its vitamin-K-binding pocket.

A cholesterol molecule interacted with GGCX transmembrane helices; structural, cellular and simulation results connected this site with regulation of cellular GGCX protein levels.

A conserved dipeptide-anchoring mechanism supports repeated glutamate carboxylation while a substrate remains associated with GGCX.

Cryo-EM structures and biochemical analyses supported a proposed bicarbonate-mediated carbon-dioxide capture model for GGCX.

Recombinantly expressed VKORC1 activity was sensitive to warfarin.

Mgp-null mice developed arterial calcification leading to vascular rupture and death within two months.

Mgp deletion caused inappropriate cartilage calcification with growth-plate abnormalities, short stature, osteopenia and fractures.

The double-knockout mice had reduced bone strength associated with disrupted mineral orientation, without a change in bone quantity in that study.

The phosphorylated serine motif also inhibited calcification and bound cell surfaces and vesicle-like structures.

Warfarin-treated vascular cells produced uncarboxylated MGP and accumulated more calcium salts than controls.

MGP Gla residues and Pro64 contributed to BMP4 binding and inhibition; only BMP4-binding-competent variants prevented osteogenic differentiation and calcification.

Calcium chelation or warfarin treatment abolished MGP binding to BMP4 in the tested system.

Functional TYRO3 activation by GAS6 in the reporter system depended on vitamin K-mediated carboxylation and phosphatidylserine engagement.

Functional AXL activation by GAS6 in the reporter system depended on vitamin K-mediated carboxylation and phosphatidylserine engagement.

Functional MERTK activation by GAS6 in the reporter system depended on vitamin K-mediated carboxylation and phosphatidylserine engagement.

Uncarboxylated GAS6 and selected domain-deletion variants retained TAM binding but acted as blocking decoy ligands rather than activators.

Osteoblast Ggcx deletion reduced multinucleated osteoclast formation and increased bone mass in six-month-old male mice.

Pharmacological inhibition of mouse-axl blocked osteoclast generation in the co-culture system.

Pharmacological inhibition of mouse-mertk blocked osteoclast generation in the co-culture system.

Increasing marrow GAS6 in transgenic male mice increased osteoclast number and size and decreased bone mass.

Vitamin K2 bound and activated human SXR and induced its CYP3A4 target gene in the tested system.

Vitamin K2 induced bone-marker expression in wild-type mouse calvarial cells but not Pxr-deficient cells.

TSKU was identified as a primary SXR target responsive to vitamin K2 and rifampicin in osteoblastic cells.

MATN2 was identified as a primary SXR target responsive to vitamin K2 and rifampicin in osteoblastic cells.

CD14 was identified as a primary SXR target responsive to vitamin K2 and rifampicin in osteoblastic cells.

Gain- and loss-of-function experiments implicated tsukushi in vitamin K2-associated collagen accumulation.

Reduced vitamin K forms trapped radicals and inhibited phospholipid peroxidation in the tested systems.

FSP1 knockout diminished MK-4 and K1 protection; wild-type FSP1 rescued protection while its myristoylation-defective G2A mutant did not.

Cells lacking both GPX4 and FSP1 required higher K1/MK-4 concentrations to prevent ferroptosis than cells lacking GPX4 alone.

A CRISPR screen independently identified FSP1 as the warfarin-resistant vitamin K reductase; FSP1 inhibition impaired vitamin K-dependent carboxylation.

DHODH did not support vitamin K-dependent carboxylation in the tested reporter system despite its separate ubiquinone-associated ferroptosis role.

The tested lipophilic statins inhibited UBIAD1 enzymatic activity in microsomal assays.

Vitamin K2 transferred electrons in Drosophila mitochondria and improved ATP production; Heix-mutant defects were rescued by K2.

Vitamin K2 entered mitochondria but restored neither respiratory electron flow nor ATP synthesis in CoQ-deficient human cells and yeast; CoQ4 did restore function.

Human VKORC1 missense variants were identified in combined vitamin K-dependent factor deficiency and in warfarin resistance; the deficiency variant did not increase VKOR activity upon overexpression.

Vkorc1-null mice died 2–20 days after birth with severe deficiency of carboxylated clotting factors and extensive hemorrhage.

Oral vitamin K rescued the lethal bleeding phenotype of Vkorc1-null mice.

The GGCX case had combined vitamin K-dependent factor deficiency; vitamin K substitution only partly normalized factor levels.

The tested bovine-f2 Gla-domain protein showed calcium-specific contact with negatively charged phospholipid monolayers.

The tested f9 Gla-domain protein showed calcium-specific contact with negatively charged phospholipid monolayers.

The tested pros1 Gla-domain protein showed calcium-specific contact with negatively charged phospholipid monolayers.

The tested bovine-proc Gla-domain protein showed calcium-specific contact with negatively charged phospholipid monolayers.

The tested proc Gla-domain protein showed calcium-specific contact with negatively charged phospholipid monolayers.

Prothrombin carboxylation normalized at 200 micrograms/day, whereas other vitamin K markers had not all returned to baseline after short repletion up to 450 micrograms/day.

Acenocoumarol increased uncarboxylated factor II, osteocalcin and dp-ucMGP and reduced endogenous thrombin generation.

MK-7 at 10 and 20 micrograms/day increased endogenous thrombin potential by approximately 20% and 30%, respectively; ucOC and dp-ucMGP did not change.

MK-7 reduced age-related loss of lumbar-spine and femoral-neck BMD/BMC, but not total-hip BMD, over three years.

With calcium and D3 in both groups, MK-7 reduced ucOC by about 65% after one year.

Adding menatetrenone to calcium did not significantly reduce new vertebral fractures in the full analysis set; the clinical-fracture secondary difference was also nonsignificant.

MK-7 produced greater one-third distal-radius BMD loss than placebo: change difference -0.023 g/cm2, 95% CI -0.039 to -0.008.