MK-7 vs MK-4
Summary
MK-7 (menaquinone-7) and MK-4 (menaquinone-4) are both vitamin K2 forms, but they have fundamentally different pharmacokinetic profiles. MK-7 is the only K homolog that meaningfully supports extrahepatic VKDP carboxylation at nutritional doses. MK-4 is rapidly cleared and is not detectable after a single oral dose at nutritional levels. All positive vascular and bone RCTs used MK-7.
Pharmacokinetic Comparison
| Parameter | MK-4 | MK-7 |
|---|---|---|
| Half-life | Very short — not detectable after single oral dose at nutritional levels | ~68–72 hours |
| Serum detection | Not detectable after single oral dose; does not accumulate with repeated nutritional dosing | Detected up to 48+ hours after single dose |
| Tmax | Rapidly cleared | 2–6 hours (formulation-dependent) |
| Distribution | Primarily hepatic (hepatic targeting) | LDL-C/VLDL-C mediated redistribution → extrahepatic tissue exposure |
| Extrahepatic VKDP carboxylation | Not effective at nutritional doses | Effective at 60–180 µg/day |
| Effective at nutritional doses | ❌ No | ✅ Yes |
| Used in positive RCTs | ❌ No | ✅ Yes (arterial stiffness, bone turnover) |
Sources: PMID 3502319, PMID 7230802, PMID 9237441
Mechanism
MK-4
MK-4 (also called menatetrenone) is synthesized in the body from vitamin K1 (phylloquinone) via partial conversion, and can also be produced from menadione (vitamin K3). At pharmacological doses (e.g., 45 mg/day used in some Japanese osteoporosis studies), MK-4 has demonstrated effects on bone metabolism. However:
- At nutritional doses (~100–200 µg/day), MK-4 is not detectable in serum after a single oral dose
- It does not accumulate with repeated nutritional-level dosing
- It is primarily hepatically distributed and does not adequately support extrahepatic VKDPs (osteocalcin, MGP) at nutritional doses
MK-7
MK-7 is a long-chain menaquinone produced by fermentation (natto is the primary dietary source). Its longer side chain allows it to:
- Incorporate into LDL-C/VLDL-C particles
- Redistribute to extrahepatic tissues (bone, vasculature)
- Provide sustained exposure to γ-glutamyl carboxylase in peripheral tissues
- Maintain effective concentrations for osteocalcin and MGP carboxylation at doses of 60–180 µg/day
Clinical Evidence
| Study | Form | Dose | Outcome | Result |
|---|---|---|---|---|
| Head-to-head PK study (PMID 3502319) | MK-4 vs MK-7 | Single dose | Serum detection | MK-4: not detectable; MK-7: detected up to 48+ hours |
| Healthy women PK study (PMID 7230802) | MK-4 vs MK-7 | Repeated dosing | Accumulation | MK-4: no accumulation; MK-7: accumulates |
| Arterial stiffness RCT (PMID 25694037) | MK-7 | 180 µg/day × 3 years | cfPWV, dp-ucMGP | ✅ Improved; dp-ucMGP ↓50% vs placebo |
| Bone turnover RCT meta-analysis (PMID 41268154) | MK-7 (majority of RCTs) | 100–360 µg/day | ucOC, bone turnover markers | ✅ Improved |
| K4Kidneys RCT (PMID 32817311) | MK-7 | 400 µg/day × 12 months | cfPWV in CKD | ❌ Null — population-specific null |
Why This Matters for Vitals
Product selection is critical. Any vitamin K2 supplement that lists “vitamin K2” without specifying MK-7 may contain MK-4, which is ineffective at nutritional doses. Users must verify the specific menaquinone form on the label.
- For bone health stack: Only MK-7 at 100–180 µg/day is supported by RCT evidence
- For vascular health stack: Only MK-7 has demonstrated arterial stiffness benefit
- For general VKDP support: MK-7 is the appropriate choice; MK-4 is not a substitute at nutritional doses
Common misleading labeling: Some products say “Vitamin K2 (menaquinone)” without specifying the MK number. Confirm it states MK-7 or menaquinone-7 specifically. “MenaQ7” is a common standardized extract name.
Related Notes
- Vitamin D3 K2 — MK-7 is the K2 form used in the D3+K2 stack
- Hypercalcemia — D3 safety context (not K2-specific)