Meta Information
ID:vitamin-k2
Name:
Schema Version:2.4_uniform_evidence_2026_06_18
Created
2026-05-21T22:30:00Z
Model
phase-a-upgrade-claude-sonnet-4.6
Interactions
Target id:
/intervention/warfarin
Target name:
Warfarin (Coumadin)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Vitamin K directly opposes the anticoagulant effect of warfarin by promoting the synthesis of clotting factors, which can lead to therapeutic failure and increased risk of blood clots.
Actionable advice:
Vitamin K2 supplements should not be taken while on warfarin unless specifically instructed and closely monitored by the prescribing physician.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
6 Aluminum Lake
10 mg: Dye-free
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Warfarin acts by inhibiting the synthesis of vitamin K-dependent clotting factors, which include
Factors II, VII, IX, and X, and the anticoagulant proteins C and S.
Label source:
Action type:
avoid
Target id:
/dietary/high-fat-meal
Target name:
Meal Containing Dietary Fat
Severity:
major
Interaction type:
requirement
Nature:
temporal
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
As a fat-soluble vitamin, Vitamin K2 requires dietary fats for proper absorption from the small intestine into the bloodstream.
Actionable advice:
Vitamin K2 should be taken with a meal that contains some healthy fat (e.g., olive oil, avocado, nuts).
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The oral bioavailability of lipid-soluble vitamin K was influenced by the fat content of a meal, although the increase in bioavailability seemed to reach a peak when the lipid content of the meal was > 35 g.
Label source:
PubMed: Journal of pharmaceutical sciences (1996)
Source url:
Exact phrase from label:
It is concluded that the bioavailability of membrane-bound phylloquinone is extremely poor and may depend on other food components, notably fat.
Label source:
PubMed: The British journal of nutrition (1996)
Source url:
Exact phrase from label:
The vitamin K2 uptake into buccal and intestinal cells was increased via micellization.
Label source:
PubMed: Nutrients (2025)
Action type:
informational_none
Target id:
/class/bile-acid-sequestrants
Target name:
Bile Acid Sequestrants (e.g., Cholestyramine)
Severity:
major
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
4
Hours after target:
1
Description:
These medications bind to bile acids in the gut, which prevents the proper absorption of fat-soluble vitamins like Vitamin K2.
Actionable advice:
Vitamin K2 should be taken at least 1 hour before or 4 hours after bile acid sequestrants.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Because cholestyramine binds bile acids, QUESTRAN may interfere with normal fat digestion
and absorption and thus may prevent absorption of fat-soluble vitamins such as A, D, E and
K.
Label source:
Action type:
separate
Target id:
/intervention/orlistat
Target name:
Orlistat (Xenical, Alli)
Severity:
major
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
2
Description:
Orlistat blocks the absorption of dietary fat, which is necessary to absorb fat-soluble vitamins like Vitamin K2.
Actionable advice:
Vitamin K2 doses and Orlistat should be separated by at least 2 hours.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
11 DESCRIPTION
11 DESCRIPTION XENICAL (orlistat) is a gastrointestinal lipase inhibitor for obesity management that acts by inhibiting the absorption of dietary fats.
Label source:
Action type:
separate
Target id:
/biomarker/inr
Target name:
INR (Prothrombin Time)
Severity:
major
Interaction type:
assay_interference
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Vitamin K2 supplementation directly opposes the effect of warfarin, causing a lower INR reading which indicates a reduced level of anticoagulation and increased clotting risk.
Actionable advice:
Vitamin K2 should not be taken while monitoring INR for warfarin therapy, unless under strict medical supervision.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The vitamin K supplement was discontinued and his warfarin dose was increased by 14.3%.
Label source:
PubMed: Elevated international normalized ratio from vitamin K supplement discontinuation. (PMID 21205949)
Action type:
monitor
Target id:
/intervention/vitamin-d
Target name:
Vitamin D3
Severity:
moderate
Interaction type:
synergistic
Nature:
temporal
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Vitamin D promotes the synthesis of proteins (e.g., osteocalcin, MGP) that Vitamin K2 then activates to properly regulate calcium placement in the body, enhancing bone and cardiovascular health.
Actionable advice:
Vitamin K2 and Vitamin D3 are best taken together with a fatty meal for optimal effect.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Exact phrase from label:
vitamin D promotes the production of vitamin K-dependent proteins, which require vitamin K for carboxylation in order to function properly
Label source:
Primary literature: https://pmc.ncbi.nlm.nih.gov/articles/PMC5613455/
Action type:
informational_none
Target id:
/intervention/vitamin-e
Target name:
Vitamin E (High Doses)
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
High supplemental doses of Vitamin E (>800 IU/day) can antagonize the effects of Vitamin K, particularly its role in blood clotting, and may impair its absorption.
Actionable advice:
Very high doses of Vitamin E are best not taken with Vitamin K2 unless directed by a physician.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Clinicians should assess patient supplementation status pre-treatment to optimize outcomes and minimize complications, particularly advising against high-dose vitamin E peri-procedurally.
Label source:
PubMed: Botulinum Toxin Effects and Its Association with Vitamin and Mineral Supplementation: A Narrative Review. (PMID 41683312)
Action type:
avoid
Target id:
/intervention/vitamin-a
Target name:
Vitamin A (High Doses)
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
High supplemental doses of Vitamin A (>10,000 IU/day) can compete with Vitamin K for intestinal absorption, potentially leading to reduced Vitamin K status.
Actionable advice:
High doses of Vitamin A are best not taken with Vitamin K2 unless medically supervised.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Vitamin A also significantly decreased the uptake of the other FSVs but, conversely, its uptake was not impaired by vitamins D and K and even promoted by vitamin E.
Label source:
PubMed: Food chemistry (2015)
Source url:
Exact phrase from label:
The fat-soluble vitamins are vitamins A, D, E, and K. Each vitamin has unique characteristics and contributes to the overall health of an individual. These vitamins have complex absorption, metabolism, and distribution elements that provide protection to the cells in the body as well as many organs.
Label source:
PubMed: The Nursing clinics of North America (2021)
Source url:
Exact phrase from label:
Vitamins, like many substances, may be toxic when taken in large quantities, especially the fat-soluble vitamins, and the concept of "more is better" is a common misconception.
Label source:
PubMed: Advances in experimental medicine and biology (1984)
Action type:
avoid
Target id:
/class/antibiotics-long-term
Target name:
Antibiotics (Long-term Use)
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Long-term use of broad-spectrum antibiotics can reduce the gut bacteria that produce some forms of Vitamin K2 (menaquinones), potentially lowering overall vitamin K status.
Actionable advice:
If on long-term antibiotics, ensure consistent intake of Vitamin K2 from supplements or food.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
CONCLUSION: These data provide direct evidence for the absorption of vitamin K2 from the distal small bowel, supporting a definite role for bacterially synthesized vitamin K2 in contributing to the human nutritional requirements of this vitamin.
Label source:
PubMed: The contribution of vitamin K2 (menaquinones) produced by the intestinal microflora to human nutritional requirements for vitamin K. (PMID 8198105)
Action type:
informational_none
Target id:
/condition/hepatic-impairment
Target name:
Severe Liver Disease
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
The liver is the primary site for synthesizing vitamin K-dependent clotting factors; in severe liver disease, this function is compromised, and response to vitamin K is unpredictable.
Actionable advice:
It is important to consult a physician before using Vitamin K2 for those with severe liver disease.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The Cmax in groups LC and CH were 85.9 and 126.3 nmol/l, respectively, which is significantly reduced compared with that of group N (184.4 nmol/l) (p less than 0.01 and p less than 0.05, respectively).
Label source:
PubMed: Scandinavian journal of gastroenterology (1990)
Source url:
Exact phrase from label:
In this situation abnormalities may be due to deficient synthesis of coagulation factors in hepatocellular failure, by failure of vitamin K absorption, and also by disseminated intravascular coagulation (DIC).
Label source:
PubMed: Clinics in haematology (1985)
Source url:
Exact phrase from label:
Vitamin K-dependent carboxylase is found in the liver, where it is involved in the synthesis of four blood coagulation factors and protein C.
Label source:
PubMed: Haematologia (1985)
Action type:
informational_none
Target id:
/intervention/magnesium
Target name:
Magnesium
Severity:
minor
Interaction type:
synergistic
Nature:
temporal
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Magnesium is an essential cofactor for the conversion and activation of Vitamin D, which in turn works synergistically with Vitamin K2 for calcium regulation.
Actionable advice:
Consider taking magnesium in the same supplement regimen as Vitamin D and K2.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
VitK2 and Mg both appear to be involved in bone metabolism. Data suggest that VitK2 supplementation might improve bone quality and reduce fracture risk in osteoporotic patients, potentially enhancing the efficacy of Ca ± vitD.
Label source:
PubMed: Maturitas (2020)
Source url:
Exact phrase from label:
In contrast, vitamin K(2) (MK-4:menatetrenone) inhibited osteoclastic bone resorption stimulated by the Mg-insufficiency, thereby normalizing bone remodeling.
Label source:
PubMed: Clinical calcium (2005)
Source url:
Exact phrase from label:
Together with D3, vitamin K2 and magnesium should be supplemented to prevent long-term health risks.
Label source:
PubMed: International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases (2020)
Action type:
informational_none
Target id:
/condition/renal-impairment
Target name:
Chronic Kidney Disease
Severity:
minor
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Vitamin K2 may help prevent vascular calcification, a common and serious complication in chronic kidney disease, by activating matrix Gla protein (MGP).
Actionable advice:
It is a good idea to talk to a nephrologist; Vitamin K2 may be beneficial but requires coordination with other treatments.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Herein, we focus on another prominent action of vitamin K, in particular vitamin K2 (namely, the activation of matrix γ-carboxyglutamic acid protein, the most potent inhibitor of cardiovascular calcifications).
Label source:
PubMed: Kidney international (2021)
Source url:
Exact phrase from label:
Matrix Gla Protein (MGP), the most potent inhibitor of VC, requires vitamin K as a co-factor to become biologically active.
Label source:
PubMed: Current vascular pharmacology (2022)
Source url:
Exact phrase from label:
Vitamin K plays different roles, including in activating vitamin K-dependent proteins (VKDPs) and in modulating bone metabolism and contributing to the inhibition of VC.
Label source:
PubMed: International journal of molecular sciences (2022)
Action type:
informational_none