What are the effects of Vitamin K2 (Menatetrenone) MK-7 on the body?

Effects of Vitamin K2 MK-7 on the Body

Vitamin K2 MK-7 (menaquinone-7) has limited evidence for clinical benefit in cardiovascular calcification prevention and bone health preservation, with multiple clinical trials showing no significant effect on coronary artery calcification progression despite its theoretical benefits. 1

Mechanism of Action

Vitamin K2 MK-7 functions primarily as a cofactor for the carboxylation of vitamin K-dependent proteins:

• Acts as a cofactor for γ-glutamyl carboxylase enzyme
• Converts undercarboxylated proteins to their active carboxylated forms:
  • Osteocalcin (OC) - for bone mineralization
  • Matrix Gla protein (MGP) - inhibits vascular calcification 1

MK-7 has distinct properties compared to other vitamin K forms:

• Longer half-life than vitamin K1 (phylloquinone) and MK-4
• Higher bioavailability than other vitamin K homologs
• Better absorbed and remains detectable in serum for longer periods (up to 48 hours) 2

Effects on Bone Health

While some research suggests potential benefits, clinical evidence shows mixed results:

• May decrease age-related decline in bone mineral density (BMD) in postmenopausal women 3
• Some evidence suggests preservation of trabecular bone microarchitecture at the tibia 4
• Upregulates osteoprotegerin, which inhibits RANK ligand and reduces bone resorption 5

However, the KDIGO guidelines note that multiple clinical trials have failed to demonstrate consistent benefits:

• Oikonomaki et al. (2019) - No difference in CAC progression with 200 mg/day MK-7
• De Vriese et al. (2020) - No difference in CAC, TAC, or AVC progression
• Levy-Schousboe et al. (2021) - No difference in cfPWV, CAC, or AAC progression
• Naiyarakseree et al. (2023) - No difference in change in cfPWV
• Haroon et al. (2023) - No difference in CAC, AVC, or PWV progression 1

Cardiovascular Effects

Despite theoretical benefits for cardiovascular health through inhibition of vascular calcification:

• Multiple clinical trials have failed to show significant effects on coronary artery calcification (CAC)
• No consistent benefit demonstrated for arterial stiffness measures
• Theoretical mechanism involves carboxylation of Matrix Gla Protein (MGP), which inhibits vascular calcification 1

Safety Profile

Vitamin K2 MK-7 has a favorable safety profile:

• Not associated with toxicity unlike synthetic vitamin K3
• No established upper limit for vitamin K2 intake
• Safe for patients with chronic kidney disease 1

Important Clinical Considerations

1. Drug Interactions: Patients using vitamin K antagonists (e.g., warfarin) should be monitored closely as MK-7 can affect anticoagulation control 1

2. At-risk populations: Vitamin K status should be measured in patients with:

   • Fat malabsorption conditions (celiac disease, cystic fibrosis, short bowel)
   • Prolonged use of broad-spectrum antibiotics
   • Chronic kidney disease 1

3. Calciphylaxis risk: Use of vitamin K antagonists in dialysis patients is associated with up to 11-fold increased risk of developing calciphylaxis 1

Dosing Considerations

• Nutritional doses of MK-7 (60-420 μg) can increase serum MK-7 levels
• MK-7 at 180-375 μg daily has been studied for bone health effects
• Clinical trials for cardiovascular outcomes have used doses ranging from 200-360 μg daily 1, 2, 3

While vitamin K2 MK-7 has theoretical benefits and some promising research, the most recent and highest quality evidence from multiple clinical trials fails to demonstrate consistent clinical benefits for cardiovascular calcification prevention, which is a key outcome related to mortality and morbidity.