Elimination Time of Menaquinone-4 (MK-4) from Plasma
MK-4 (menatetrenone) at a dose of 5,000 micrograms is rapidly eliminated from plasma and is typically undetectable in serum within hours after administration.
Pharmacokinetics of MK-4
Research on MK-4 bioavailability shows that this form of vitamin K2 has extremely poor bioavailability and a very short half-life in plasma:
- MK-4 is not detectable in serum after single-dose administration, even at doses much higher than 5,000 micrograms 1
- In a study comparing MK-4 and MK-7, researchers administered a single dose of 420 μg (945 nmol) of MK-4 to healthy Japanese women and found that MK-4 was not detectable in the serum of any subjects at any time point after administration 1
- Even with consecutive daily administration of MK-4 (60 μg) for 7 days, there was no increase in serum MK-4 levels 1
Dose-Response Studies
Studies examining various doses of MK-4 have found:
- When administered at 1.5 mg (1,500 micrograms) daily, MK-4 shows biological effects on osteocalcin carboxylation within 2 weeks, but serum levels are typically not measured due to rapid clearance 2
- Higher doses of MK-4 (5 mg and 45 mg) show similar effects on reducing undercarboxylated osteocalcin, suggesting that even at higher doses, MK-4 is rapidly metabolized 3
- Low-dose MK-4 supplementation (1.5 mg daily) for 12 months shows beneficial effects on bone metabolism markers despite its rapid clearance from plasma 4
Clinical Implications
The rapid elimination of MK-4 from plasma has important implications:
- Despite being undetectable in serum, MK-4 still exerts biological effects on bone metabolism 3, 4
- The therapeutic effects of MK-4 on bone health appear to be dose-dependent up to 5 mg, with no additional benefit seen at 45 mg doses 3
- For clinical use in osteoporosis treatment, MK-4 is typically administered at much higher doses (45 mg) and in multiple daily doses to compensate for its poor bioavailability 5
Summary
Based on the available evidence, 5,000 micrograms (5 mg) of MK-4 is likely eliminated from plasma within hours after administration, and would be undetectable in serum shortly thereafter. This rapid elimination explains why MK-4 is typically administered in multiple daily doses when used therapeutically for conditions like osteoporosis.