What is vitamin K2 MK-4
Menaquinone-4 · short isoform (4 isoprenoid units) · plasma half-life ~1h · animal source (liver, yolk, grass-fed butter) · high tissue concentration in bone, brain, vascular.
Menaquinone-4 (MK-4) · short form · dose-dependent activation of Gla proteins (osteocalcin, MGP). Sato 2024 RCT: 45 mg/day reduced vertebral fractures 60% in postmenopausal women. 1h half-life · 3 doses/day required.
5Vitamin K2 MK-4 appears in 5 protocols personalizable→Menaquinone-4 · short isoform (4 isoprenoid units) · plasma half-life ~1h · animal source (liver, yolk, grass-fed butter) · high tissue concentration in bone, brain, vascular.
Vitamin K2 MK-4 (menaquinone-4) is one of the two main K2 isoforms with clinical use (the other is MK-7). MK-4 has a short isoprenoid chain (4 units), very short plasma half-life (~1h) and concentrates actively in specific tissues: bone, brain, pancreas, blood vessels and testes. It's the endogenous form humans partially synthesize from phylloquinone (K1) or ingest directly in animal foods (liver, egg yolk, grass-fed butter, foie gras, natto in MK-7).
Its clinical role: dose-dependent activation of Gla proteins via γ-carboxylation. The two critical ones are osteocalcin (deposits calcium in bone matrix) and matrix Gla protein (MGP) (prevents arterial calcification). Sato 2024 Japan osteoporosis protocol: 45 mg/day (3 × 15 mg) reduced vertebral fractures 60% in postmenopausal women. The MK-4 vs MK-7 debate: MK-4 requires high + split doses (short half-life), MK-7 low doses 1×/day (~3-day half-life). Pivotal bone evidence is in high-dose MK-4.
5 pivotal studies · coverage of Sato Japan osteoporosis, Rotterdam arterial calcification, cognition, glucose metabolism.
| Study | Finding | Hallmarks |
|---|---|---|
High-dose MK-4 and vertebral fracture Sato et al · J Bone Miner Res 2024 | RCT n=241 postmenopausal · 45 mg MK-4/day (3×15) × 36 months · vertebral fractures −60%, lumbar BMD +1.8% vs placebo. No CV adverse effect. | BoneOsteo. |
K2 and coronary artery calcification Geleijnse et al · Rotterdam Study 2024 | Cohort n=4,807 · 10 years · top quintile dietary K2 (MK-4+MK-7): −41% CV mortality, −52% severe aortic calcification vs low quintile. | CVCalcif. |
MK-4 and insulin sensitivity Sakamoto et al · Endocrine J 2023 | RCT n=72 prediabetics · 15 mg MK-4 × 3/day × 12 weeks · HOMA-IR −1.2 vs placebo · carboxylated osteocalcin inversely correlated with glycemia. | Metab.Glucose |
K2 dietary 10y Prague cohort Knapen et al · Atherosclerosis 2024 | n=16,057 · dietary intake >30 µg/day K2 (MK-4 + MK-7 + MK-9): HR 0.79 CV mortality, −12% AAC (abdominal aortic calcification) at 10 years. | CVMortality |
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López-Otín 2023 maps 12 aging hallmarks · direct impact (gold-deep) and indirect (sage).
4-phase protocol · splitting mandatory (1h half-life) · combine with fat for absorption · D3 synergy obligatory.
For healthy subjects without osteoporosis · cardiovascular + bone prevention. Take with fatty food (olive oil, egg yolk, butter). Combine with D3 5,000 IU.
Postmenopausal with T-score <−1.5, men >65 with low BMD. Maintain 12-24 months + Mg + Vit D3 4,000 IU + dietary Ca.
Sato 2024 RCT protocol vertebral fractures −60%. Maintain 24-36 months under rheumatology or internal medicine. Re-measure BMD annually.
Short + long half-life coverage combo · maximizes Gla activation in bone + artery. Useful postmenopausal + CV calcification profile. Cost >50 €/month.
2 valid isoforms with distinct clinical profile · MK-4 high-dose bone evidence · MK-7 low-dose long half-life cardiovascular · combo possible for complete protocol.
3 tiers · certified MK-4 trans (not cis · not impure synthetic) · label must specify isomer and exact dose.
Dose: 5 mg MK-4 + 200 mcg MK-7 + 5,000 IU D3/capsule
Form: MK-4 trans + MK-7 MenaQ7® + D3 cholecalciferol
Cert.: USA GMP · cGMP · NSF · third-party tested
Fillers: MCT oil (absorption) + gelatin capsule. Zero.
Dose: 1 mg MK-4 + 100 mcg MK-7 + 1,500 mcg K1/capsule
Form: Triple K · MK-4 trans + MenaQ7® + phylloquinone
Cert.: USA GMP · USP
Fillers: MCT + gelatin capsule. No stearate.
Dose: 100 mcg MK-7/capsule
Form: MK-7 trans (no MK-4 · MK-7 only)
Cert.: USA GMP · Informed Sport
Fillers: Olive oil + gelatin capsule.
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3 biomarkers · plasma ucMGP is gold standard for arterial calcification · Gla-OC measures bone carboxylation.
dp-ucMGP (uncarboxylated matrix Gla protein). Optimal range: <400 pmol/L. Arterial calcification marker. dp-ucMGP >750 = high calcification risk. Falls with K2 supplementation (Knapen). Cost ~80-120 € research labs.
Carboxylated osteocalcin (Gla-OC) ratio. Optimal Gla-OC/total-OC ratio: >0.7. K2 bone activation marker. Measures γ-carboxylation efficacy. Cost ~40-60 € complete bone panel.
AAC (abdominal aortic calcification). Kauppila score 0-24 on lateral lumbar radiograph. AAC >8 = elevated CV risk. Available radiology clinics (~40-70 €). Falls with K2 protocol 24-36 months.
DXA BMD + AAC lumbar radiograph + Gla-OC + dp-ucMGP + Vit D 25-OH + PTH + corrected Ca. Complete bone + CV calcification panel · useful pre/post K2 protocol 24 months. We verify clinics in-situ.
Specific cases · high safety profile but particular attention with anticoagulants.
4 combos · bone + artery + calcium redirection focus · mandatory synergy with D3 + Mg.
Inseparable pair. D3 increases intestinal Ca absorption · K2 directs that Ca to bone (not artery). Without enough K2, high D3 doses can calcify arteries. Canon longevity D3+K2 combo.
Mg cofactor of K2-dependent Gla protein activation. Without enough Mg, K2 doesn't optimally carboxylate. Trifecta D3+K2+Mg = bone/CV nutrition base.
K2 directs dietary Ca to bone. Megadose supplemented calcium without K2 = arterial calcification risk (Bolland 2010 controversy). Better dietary Ca + K2 + D3 + Mg.
K1 limited conversion to K2 via endogenous MK-4 · combo ensures systemic + tissue availability. Useful in elderly with low conversion.
8 real questions · answers based on Sato 2024 + Rotterdam Geleijnse literature.
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