Vitamin K2 (MK7) Clinical Evidence

British Journal of Nutrition
Brugè, F., et al. Olive oil supplemented with menaquinone-7 significantly affects osteocalcin carboxylation. 2011 Oct; 106(7):1058
62.

Topic:

Can MK-7-enriched olive oil increase blood levels of MK-7 and affect the carboxylation of osteocalcin, a bone protein?

Background:

Menaquinone-7 (MK-7) is a type of vitamin K that enhances carboxylation, a chemical reaction within bone protein that is necessary for this protein to function.

Study Type:
Human clinical intervention trial

Study Design:
Subjects took plain olive oil, then olive oil with MK-7 in 2 increasing doses, with washout periods between. Researchers collected and tested blood samples.

Subjects:

12 healthy young volunteers

Dosage:

45 mcg for 2 weeks followed by 90 mcg for 2 weeks

Results:

Olive oil alone had no effect on MK-7 levels, but olive oil with MK-7 increased blood levels of MK-7 significantly and in a dose-dependent manner. 

  • The higher dose significantly increased carboxylated osteocalcin and decreased under-carboxylated osteocalcin.

Conclusion:

“We conclude that regular consumption of MK-7enriched olive oil may constitute a valid approach in order to preserve some key biochemical mechanisms controlling bone mineralisation.”

Blood
Schurgers, L.J., et al. Vitamin-K containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7. 2007 Apr; 109(8):327983.

Topic:

What is the comparative absorption and efficacy of synthetic vitamin K1 and MK-7 (a form of vitamin K2)?

Background:

Vitamin K has multiple uses in the body.  It is necessary for the manufacture of blood coagulation factor in the liver, osteocalcin (a bone protein), and matrix Gla protein in cartilage and blood vessel walls.  Synthetic vitamin K1 is widely used in supplements. Is MK-7 a better choice?

Study Type:
Human clinical intervention trial

Study Design:

Subjects took either vitamin K1 or MK-7 and researchers collected and analyzed blood samples.

Subjects:

Healthy volunteers, ages 25-35. There were 4 phases of the study; each phase had between 10 and 18 subjects.

Dosage:

Vitamin K7 oil and vitamin K1 were mixed to a final concentration of 100 mg/L, and this mixture was given at increasing dosages (50, 100, 150, 200, 250, 300, and 500 μg each of the 2 vitamins) together with a standard breakfast.

Results:

Both forms of vitamin K were well absorbed and showed peak concentrations at 4 hours. However, MK-7 stayed in the bloodstream longer, resulting in more stable levels of vitamin K over time.  

  • It also accumulated to higher levels (700%800% higher) after prolonged supplementation. 
  • Not surprisingly, MK-7 supplementation resulted in greater carboxylation of osteocalcin than vitamin K1. (Carboxylation is a chemical reaction of osteocalcin necessary for it to function.)

Conclusion:

“A major difference between the 2 vitamin K species is the very long half-life time of MK-7, resulting in much more stable serum levels, and accumulation of MK-7 to higher levels (7- to 8-fold) during prolonged intake. MK-7 induced more complete carboxylation of osteocalcin, and hematologists should be aware that preparations supplying 50 mug/d or more of MK-7 may interfere with oral anticoagulant treatment in a clinically relevant way”.

American Journal of Kidney Diseases
Westenfeld, R., et al. Effect of vitamin K2 supplementation on functional vitamin K deficiency in hemodialysis patients: a randomized trial. 2012 Feb; 59(2):18695.

Topic:

Can vitamin K supplementation improve the function of vitamin K-dependent proteins in hemodialysis patients?

Background:

Vascular calcification, or deposits of calcium within blood vessels, is a condition associated with cardiovascular disease and is common among kidney patients undergoing dialysis. Matrix Gla protein (MGP) inhibits this calcification but it needs to be carboxylated (a chemical reaction) to function and it needs vitamin K to do this. Osteocalcin, a bone-building protein, also requires vitamin K for carboxylation, and prothrombin (PIVKA-2), a blood coagulation factor, is elevated in the absence of vitamin K. All these factors can be used to detect vitamin K deficiency.

Study Type:
Human clinical intervention trial

Study Design:

Randomized, non-placebo-controlled trial with 3 parallel groups. Subjects in the treatment group took vitamin K2 and both groups provided blood samples for analysis.

Subjects:

53 long-term, stable, adult hemodialysis patients, 50 healthy adults as controls

Dosage:

45, 135, or 360 mcg/day for 6 weeks

Results:

At base line, the dialysis patients had 4.5 times the uncarboxylated MGP levels and 8.4 times as much uncarboxylated osteocalcin compared with the members of the control group. 

  • PIVKA-2 was elevated in 49 of the 53 members of the treatment group. After vitamin K supplementation, uncarboxylated MGP, uncarboxylated osteocalcin, and PIVKA-2 all decreased in a dose-dependent manner.  
  • The response rate for MGP levels was 77% for the middle dose and 93% for the highest dose.

Conclusion:

“This study confirms that most hemodialysis patients have a functional vitamin K deficiency. More importantly, it is the first study showing that inactive MGP levels can be decreased markedly by daily vitamin K(2) supplementation. Our study provides the rationale for intervention trials aimed at decreasing vascular calcification in hemodialysis patients by vitamin K supplementation.”

Atherosclerosis 
Buelens, J.W.J., et al. High dietary menaquinone intake is associated with reduced coronary calcification. 2009 Apr; 203(2):48993.

Topic:

Can vitamin K2 (menaquinone) reduce coronary calcification? Is it superior to vitamin K1 (phylloquinone) in this respect?

Background:

Previous research has shown that vitamin K can reduce the risk of cardiovascular disease by decreasing coronary calcification (buildup of plaque in coronary arteries), but results have been mixed. This may be because there are two forms of vitamin K, phylloquinone and menaquinone, which may have different effects.

Study Type:

Human clinical intervention trial

Study Design:

Observational study. Subjects filled out a dietary questionnaire and were tested for coronary calcification.

Subjects:

564 postmenopausal women

Dosage:

45, 135, or 360 mcg/day for 6 weeks

Results:

Coronary calcification was found in 62% of the group.

  • Higher menaquinone intake was associated with decreased risk of calcification, but phylloquinone intake was not.

Conclusion:

“This study shows that high dietary menaquinone intake, but probably not phylloquinone, is associated with reduced coronary calcification. Adequate menaquinone intake could therefore be important to prevent cardiovascular disease.”

Nutrition, Metabolism and Cardiovascular Disease
Gast, G.C., et al. A high menaquinone intake reduces the incidence of coronary heart disease. 2009 Sep; 19(7):50410.

Topic:

Can vitamin K2 (menaquinone) reduce the incidence of heart disease?

Background:

Vitamin K-dependent proteins are thought to inhibit vascular calcification and improve cardiovascular health. How do vitamins K1 and K2 compare?

Study Type:

Observational study

Study Design:

Researchers analyzed food frequency questionnaires to determine vitamin K1 and K2 intake, and adjusted for CHD risk factors and other dietary factors, and compared the dietary data with the incidence of CHD in the group.

Subjects:

16,057 women who participated in the Prospect-EPIC study between 1993 and 1997, who were ages 4970 and free of cardiovascular disease at base line

Results:

The average vitamin K2 intake was 29.1 +/- 12.8 mcg/day.  

  • Higher levels of vitamin K2 were associated with reduced risk of CHD, but the same was not true for vitamin K1. 

Conclusion:

“A high intake of menaquinone, especially MK-7, MK-8, and MK-9, could protect against CHD.”

Mechanism of Action

Vitamin K modifies several proteins, such as osteocalcin, that promote calcium uptake and bone mineralization. MK-7, a form of vitamin K2, has a very long half-life, resulting in more stable levels in the bloodstream and higher accumulation, up to 700-800% higher after prolonged intake. MK-7 also triggers a more complete carboxylation of osteocalcin.