Vitamin K2 (MK-4)
Also known as: Menaquinone-4, MK-4, Menatetrenone
Vitamin K2, specifically menaquinone-4 (MK-4), is a vital fat-soluble vitamin involved in the carboxylation of specific protein residues, notably osteocalcin and matrix Gla protein (MGP). These carboxylated proteins are crucial for directing calcium to bones and teeth and preventing its deposition in soft tissues like arteries. While its role in bone mineral density and fracture prevention is well-established, growing evidence supports its benefits for cardiovascular health by inhibiting arterial calcification. MK-4 typically has a shorter half-life than longer-chain menaquinones like MK-7, necessitating more frequent dosing for sustained activity.
Last reviewed: 2026-04-22 · 3 indexed studies
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Overview
Vitamin K2 (menaquinone-4, MK-4) is one of the forms of vitamin K, a fat-soluble vitamin essential for blood clotting and bone health. While vitamin K1 (phylloquinone) is found primarily in leafy green vegetables and is crucial for coagulation, vitamin K2 encompasses a group of menaquinones (MK-n) mostly found in animal products and fermented foods, playing a significant role in calcium metabolism and cardiovascular health. MK-4 is a short-chain menaquinone and is the most common form of vitamin K2 found in the body's tissues, primarily through conversion from vitamin K1.
Mechanism & Function
Menaquinone-4 (MK-4) · C₃₁H₄₀O₂ — source: PubChem CID 5282367
Golden-yellow vitamin K2 oil. Short half-life — divided dosing recommended.
- Softgel
- Capsule
- Liquid
Softgel is generally preferred for bioavailability or efficacy.
Mechanism of Action
Vitamin K2 acts as a cofactor for gamma-glutamyl carboxylase, an enzyme that carboxylates glutamate residues on vitamin K-dependent proteins (VKDPs). This carboxylation is necessary for VKDPs to become biologically active. Key VKDPs include osteocalcin, vital for bone mineralization, and matrix Gla protein (MGP), which inhibits soft tissue calcification, particularly in the vasculature. MK-4's rapid turnover suggests it may have a more localized or transient impact compared to longer-chain menaquinones.
Physiological Role
Vitamin K2's primary physiological role is in post-translational modification of VKDPs, ensuring their proper function. In bone metabolism, it activates osteocalcin, facilitating calcium binding and incorporation into the bone matrix. In cardiovascular health, it activates MGP, which chelates calcium and prevents its deposition in arterial walls. It also has a role in cell growth, metabolism, and neurological function, although these areas are less extensively studied compared to its bone and cardiovascular effects.
Primary Pathways
Performance / Health Relevance
Vitamin K2 (MK-4) is primarily relevant for long-term health, particularly bone integrity and cardiovascular function. For athletes, maintaining strong bones is crucial for injury prevention and overall structural support. Preventing arterial calcification contributes to cardiovascular health, which is fundamental for exercise performance and recovery, although direct acute performance enhancements are not typically expected from K2 supplementation.
Evidence Review
Compare Vitamin K Forms
Full comparison3 vitamin k forms are indexed. Bioavailability, clinical evidence, and best-use cases differ meaningfully between them.
| Form | Evidence |
|---|---|
Vitamin K2 (MK-4)This page MK-4 has a relatively short half-life compared to MK-7, requiring more frequent or higher dosing for sustained tissue levels. It is highly bioavailable when consumed with fat. | 70/100 |
| Vitamin K2 (MK-7) MK-7 has excellent bioavailability and a significantly longer half-life (approx. 72 hours) compared to K1 and other K2 forms, leading to more stable serum concentrations and sustained action. | 75/100 |
| Vitamin K1 (Phylloquinone) Fat-soluble vitamin; absorption is enhanced by dietary fat. Bioavailability from food sources, especially green leafy vegetables, can be variable due to entrapment within chloroplasts. | 65/100 |
Practical Use & Dosage
- Minimum Effective Dose
- 1.5 mg
- Optimal Range
- 1.5 - 15 mg
- Upper / Caution Level
- No observed adverse effect level (NOAEL) for MK-4 identified at very high doses in human studies. However, caution is advised with anticoagulant medications (e.g., warfarin).
- Timing
- With a meal containing fat to enhance absorption.
- Best Format
- Capsule or softgel for consistent dosing and absorption.
- Bioavailability
- MK-4 has a relatively short half-life compared to MK-7, requiring more frequent or higher dosing for sustained tissue levels. It is highly bioavailable when consumed with fat.
- Absorption Considerations
- Co-ingestion with dietary fat significantly improves absorption. Bile salts are essential for its emulsification and assimilation in the small intestine.
Safety & Interactions
Side Effects
- •Generally well-tolerated. Very rare cases of gastrointestinal upset at extremely high doses.
Contraindications
- Individuals on warfarin or other anticoagulant medications.
Drug Interactions
- •Warfarin (coumadin) and other vitamin K antagonists: K2 supplementation can counteract the effects of these drugs, necessitating careful medical supervision and dose adjustment.
- •Broad-spectrum antibiotics: May reduce gut bacterial production of K2 (though MK-4 is primarily converted from K1 rather than produced by gut bacteria).
- •Orlistat: May reduce absorption of fat-soluble vitamins, including K2.
Who Should Avoid
- •Individuals taking anticoagulant medications like warfarin without medical supervision.
Monitoring
Patients on anticoagulant therapy should have their INR regularly monitored if supplementing with Vitamin K2. For others, no specific monitoring is typically required.
Frequently Asked Questions
Auto-generated from indexed evidence — dosage, safety, interactions, and more.
When is Vitamin K2 (MK-4) typically used or indicated?
Vitamin K2 (MK-4) is most commonly used for: Bone health, Cardiovascular health, Calcium metabolism. Vitamin K2's primary physiological role is in post-translational modification of VKDPs, ensuring their proper function. In bone metabolism, it activates osteocalcin, facilitating calcium binding and incorporation into the bone matrix. In cardiovascular health, it activates MGP, which chelates calcium and prevents its deposition in arterial walls. It also has a role in cell growth, metabolism, and neurological function, although these areas are less extensively studied compared to its bone and cardiovascular effects.
How does Vitamin K2 (MK-4) work?
Vitamin K2 acts as a cofactor for gamma-glutamyl carboxylase, an enzyme that carboxylates glutamate residues on vitamin K-dependent proteins (VKDPs). This carboxylation is necessary for VKDPs to become biologically active. Key VKDPs include osteocalcin, vital for bone mineralization, and matrix Gla protein (MGP), which inhibits soft tissue calcification, particularly in the vasculature. MK-4's rapid turnover suggests it may have a more localized or transient impact compared to longer-chain menaquinones.
What is the recommended dose of Vitamin K2 (MK-4)?
The optimal range is 1.5 - 15 mg. with a minimum effective dose of 1.5 mg. Best taken: With a meal containing fat to enhance absorption.. Upper / caution level: No observed adverse effect level (NOAEL) for MK-4 identified at very high doses in human studies. However, caution is advised with anticoagulant medications (e.g., warfarin)..
What are the side effects of Vitamin K2 (MK-4)?
Reported side effects include: Generally well-tolerated. Very rare cases of gastrointestinal upset at extremely high doses.. Monitoring: Patients on anticoagulant therapy should have their INR regularly monitored if supplementing with Vitamin K2. For others, no specific monitoring is typically required.
Does Vitamin K2 (MK-4) interact with medications?
Known or theoretical interactions: Warfarin (coumadin) and other vitamin K antagonists: K2 supplementation can counteract the effects of these drugs, necessitating careful medical supervision and dose adjustment.; Broad-spectrum antibiotics: May reduce gut bacterial production of K2 (though MK-4 is primarily converted from K1 rather than produced by gut bacteria).; and Orlistat: May reduce absorption of fat-soluble vitamins, including K2.. Always check with a clinician before combining with prescription medication.
Who should avoid Vitamin K2 (MK-4)?
Vitamin K2 (MK-4) is generally not recommended for: Individuals taking anticoagulant medications like warfarin without medical supervision.; and Individuals on warfarin or other anticoagulant medications..
How strong is the evidence for Vitamin K2 (MK-4)?
Evidence level: Moderate (overall score 70/100), based on 3 indexed studies on SuppIndex.
Research & References (3)
Vitamin K2 (menaquinone-4) supplementation for preventing bone loss in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials
This meta-analysis investigated the effects of MK-4 supplementation on bone mineral density (BMD) and fracture incidence in postmenopausal women. It concluded that MK-4 significantly improved vertebral BMD and reduced the risk of vertebral fractures.
Effect of menaquinone-4 on the content of gamma-carboxylated osteocalcin in serum and bone in severe immobilization osteoporosis
This study examined the effect of MK-4 on osteocalcin carboxylation in patients with severe immobilization osteoporosis. It found that MK-4 supplementation increased the proportion of carboxylated osteocalcin.
Vitamin K2 (menaquinone) in soft tissue calcification: evidence from clinical and experimental studies
This review summarizes evidence on vitamin K2's role in preventing and regressing soft tissue calcification, particularly arterial calcification. It highlights MK-4's involvement in activating matrix Gla protein (MGP).
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Research Overview
Moderate EvidenceCite this ingredient
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Stable URL
https://thesuppindex.com/ingredients/vitamin-k2-mk-4
SuppIndex. (2026). Vitamin K2 (MK-4): Evidence summary, dosage and clinical studies. Retrieved October 23, 2026, from https://thesuppindex.com/ingredients/vitamin-k2-mk-4
Based on 3 indexed studies · Evidence level: Moderate.
Goal Ratings
Stack Compatibility
Often stacked with Vitamin D3, calcium, and magnesium due to their synergistic roles in bone health and calcium metabolism. Avoid stacking with warfarin.