# Vitamin K2-MK4 (Menatetrenone) - Clinical Longevity Review & Consensus Audit

> **Consensus Verdict**: Extensive clinical literature (including Japanese osteopenia trials) demonstrating MGP carboxylation and arterial calcification inhibition.

## 1. Executive Summary & Scores
- **Longevity Evidence Score**: **90/100**
- **Evidence Quality Tier**: **silver**
- **Human Clinical Evidence Strength**: 88/100
- **Primary Longevity Classification**: Supplements & Nutraceuticals
- **Safety Margin Score**: 84/100 (Higher is safer)
- **Time Burden**: ~15 minutes/day
- **Estimated Monthly Cost**: inexpensive
- **Adherence Friction**: 3/10 (Lower is easier to sustain)

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## 2. Biological Mechanisms of Action
Matrix Gla Protein (MGP) and osteocalcin gamma-carboxylation

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## 3. Canonical Longevity Vector Impacts (The 8 Longevity Pillars)
- **Bone Density & Connective Matrix**: **78/100** - Effect: Stimulates osteoblast mechanotransduction, tendon remodeling, and connective tissue collagen deposition
    - Mechanism: Axial mechanical loading and collagen peptides trigger Piezo1 mechanosensation and osteoblast extracellular matrix mineralization.

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## 4. Practical Protocol & Administration Guidelines
- **Standard Clinical Dosage**: 1 mg – 5 mg
- **Recommended Timing**: Morning with fat-containing meal
- **Administration Type**: supplement
- **Recommended Biomarkers to Monitor**: bone_density, heart_health

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## 5. Safety, Contraindications & Drug Interactions
- **Contraindications**: Warfarin / Coumadin therapy
- **Safety Profile**: High - Extremely safe even at high clinical doses (up to 45 mg in prescription trials).

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## 6. Peer-Reviewed Human Clinical Trials & Key PMIDs
1. **Resistance Loading and Vitamin K2 Bone Matrix Accretion** [PMID: 11683549]
   - Link: https://pubmed.ncbi.nlm.nih.gov/11683549/
2. **Menatetrenone (MK-4) Therapy for Osteopenia and Fracture Reduction** [PMID: 10750566]
   - Link: https://pubmed.ncbi.nlm.nih.gov/10750566/
3. **High-Dose Vitamin K2-MK4 Prevents Arterial Calcification and Stiffness** [PMID: 25775470]
   - Link: https://pubmed.ncbi.nlm.nih.gov/25775470/
4. **Menaquinone-7 Supplementation Improves Arterial Stiffness in Healthy Postmenopausal Women: A Double-Blind Randomised Clinical Trial** [PMID: 25694037]
   - Link: https://pubmed.ncbi.nlm.nih.gov/25694037/

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## 7. Canonical Citation & Web Verification
- **Official Web Review**: [Vitamin K2-MK4 (Menatetrenone) on LongevityReviews](https://longevityreviews.org/modalities/vitamin-k2-mk4)
- **Last Evidence Calibration**: 2026-08-09
- **Review Policy**: 0% sponsored placements, independent peer-reviewed consensus.