Vitamin K2 (Menaquinone)
fat-soluble
Key Takeaways
- Group of menaquinones (MK-4 to MK-13) from bacteria and fermented foods
- FDA daily value for vitamin K is 120 mcg (shared with K1)
- More effectively reaches extrahepatic tissues than K1
- MK-7 has longest half-life and greatest potency
- RCT evidence for nocturnal leg cramps and bone preservation
Evidence Spectrum
14 studies reviewed →Nocturnal leg cramp reduction
Multicenter double-blind placebo RCT (n=199, 65+): MK-7 180 mcg/day for 8 weeks reduced weekly cramps from 2.60 to 0.96 vs placebo 3.63 (P<0.001). No adverse events.1
Bone health and microarchitecture
3-year RCT (n=244): MK-7 180 mcg/day decreased BMD decline. 12-month RCT (n=148): MK-7 375 mcg/day preserved trabecular microarchitecture at tibia.3
Arterial stiffness prevention
Double-blind placebo RCT in K-deficient kidney transplant recipients (n=40): MK-7 360 mcg/day prevented arterial stiffness progression.2
Depression in PCOS
Single RCT (n=84): MK-7 90 mcg/day improved depression scores in PCOS women.4
Vascular calcification in hemodialysis
Dose-finding study (n=200): MK-7 360-1080 mcg thrice weekly reduced dp-ucMGP by 17-46%.5
14
Studies Reviewed
120 mcg
RDA (Adults (FDA Daily Value, total vitamin K))
fat-soluble
Solubility
Role in the Body
Vitamin K2 (menaquinone) comprises MK-4 through MK-13. Unlike K1, K2 reaches extrahepatic tissues (bone, arteries) regulating MGP and osteocalcin (pmid:21088475). MK-7 has longest half-life and highest bioavailability (pmid:35774605, pmid:26908424). Supplementation dose-dependently reduces inactive ucMGP and ucOC (pmid:24285428, pmid:27625301).
- Activates MGP to inhibit vascular calcification
- Activates osteocalcin for bone mineralization
- Supports blood coagulation
- Upregulates osteoprotegerin
- Suppresses proinflammatory mediators
- MK-4 induces apoptosis in cancer cell lines
Supplement Forms
MK-7 (menaquinone-7)
RecommendedBioavailability: 0.9%
Longest half-life; most studied; from natto fermentation (pmid:35774605)
MK-4 (menatetrenone)
RecommendedBioavailability: 0.3%
Shorter half-life; used at 45 mg/day in Japan for osteoporosis (pmid:18484089)
MK-7 in dairy matrix
RecommendedBioavailability: 0.95%
Yogurt with MK-7 showed enhanced absorption vs capsules (pmid:26908424)
Food Sources
Natto (richest MK 7 source)
Hard/aged cheeses (Gouda, Brie)
Egg yolks
Chicken
Grass Fed butter
Sauerkraut
Fermented dairy (yogurt, kefir)
Deficiency
Prevalence: Common, especially without fermented foods. Hemodialysis patients have high inactive MGP inversely correlated with menaquinone intake (pmid:24285428, pmid:21088475).
Symptoms:
- Elevated undercarboxylated osteocalcin
- Elevated dp-ucMGP
- Impaired bone mineralization
- Accelerated vascular calcification in CKD
Risk Factors:
- Low fermented food intake
- Chronic kidney disease (pmid:24285428, pmid:35563672)
- Kidney transplant recipients (pmid:36695702)
- Postmenopausal women
- Anticoagulant therapy
Safety & Interactions
Possible Side Effects:
- • No adverse events in trials up to 375 mcg/day for 12 months (pmid:27625301, pmid:39466236)
Drug Interactions:
- • Warfarin: interferes with anticoagulant control
Contraindications:
- • Warfarin patients should not supplement without medical supervision
Frequently Asked Questions
K2 vs K1?
K2 reaches bone and arteries more effectively than K1, activating osteocalcin and MGP.
Best form of K2?
MK-7 has longest half-life and best bioavailability. Effective at 90-375 mcg/day.
K2 for leg cramps?
RCT showed MK-7 180 mcg/day significantly reduced nocturnal leg cramp frequency in adults 65+.
Research Sources
15 peer-reviewed studies analyzed from PubMed. 5 directly cited in this review.