As seen in the diagrams below, the TRANS forms are configured as straight lines, while the CIS forms are configured as "L" shapes.

Like a master "skeleton" key, the straight shaped TRANS forms can unlock (activate) ALL Vitamin K-dependent proteins they encounter, while the L-shaped CIS forms can NOT activate ANY.

This is why, if you are going to take a Vitamin K2 supplement, regardless of whether its MK-4 or MK-7, its so important to find one that contains the highest percent possible of TRANS form isomers, otherwise you will likely receive much less bioactive Vitamin K2, than you might think (and need).

The problem is that most Vitamin K2 product manufacturers don't even disclose how much TRANS and CIS forms are present in their product. In many cases they may not even know. Most products probably contain greater than 50% TRANS form, however Vitamin K2 supplements analyzed at the University of Oslo, revealed that some MK-7 products contained as little as 15% TRANS form, which is very much at odds with their "usable K2" label claim.

• The bottom line is that the the form of MK-4 and or MK-7 you take is critical.
• TRANS form is bioactive
• CIS form is NOT bioactive.

• vK2 contains:
  • "pharmaceutical grade" Vitamin K2 (yellow color)
  • very high percent of TRANS form
  • MK-4 (100% TRANS form)
  • MK-7 (70% TRANS form)

  As can be seen (in the photo below), vK2 is yellow.

  If the vitamin K2 you take is NOT yellow . . .

  • it is NOT pharmaceutical grade
  • it is more than likely a low quality product containing Chinese ingredients
  • with a low percentage of the bioactive "trans" form.
  

VKDP's can be activated by both Vitamin K1 and K2.

• Vitamin K1 activates VKDP's in the liver to synthesize coagulation factors.
• DCP (Des-gamma-carboxy Prothrombin)
• Vitamin K2 activates VKDP involved in shuttling calcium:
• MGP (Matrix GLA protein)
• secreted by arterial linings.
• blocks calcification of heart valves, arterial walls, kidney stones
• Osteocalcin (OC or BGLAP)
• secreted by osteocytes in the bones.
• increases bone density
• Vitamin K2 activates VKDP's in the brain:
• Gas6 (Growth arrest-specific 6)
• regulates cell survival of neurons and glial cells.
• modulates sphingolipid metabolism.
• PROS1 (Protein S)
• regulates self-renewal of neural stem and progenitor cells (NSPCs).
• chemotaxis, mitogenesis, and cell growth
• Vitamin D3 consumption stimulates the secretion of MGP, OC and other VKDP's.
• Vitamin K2 demand increases with Vitamin D3 consumption.

• Vitamin K2 status biomarkers.
• uncarboxylated (unactivated) VKDP's (ucVKDP) in the blood.
• Nearly all studies today quantify vitamin K status with this method.
• higher uncarboxylated concentrations reflect lower vitamin K status.
• ucOC (undercarboxylated form of osteocalcin)
• a nutritional biomarker reflective of vitamin K status
• an indicator of bone health
• an active hormone that mediates glucose metabolism in experimental studies.
• dp-ucMGP (dephosphorylated uncarboxylated MGP)
• Assays that measure total circulating MGP (regardless of its carboxylation status) have been available for some time.
• Recently, assays that measure different fractions of MGP in circulation have been developed, of which dephosphorylated uncarboxylated MGP (dp-ucMGP) best reflects vitamin K status.
• Nowadays, dp-ucMGP is available as a fully automated commercial assay, which makes it a feasible marker as routine laboratory assessment in clinical practice.
• serum Vitamin K2 level in the blood
• Has very little usefulness:
• MK-4 is the only vitamin K2 form that can be detected for those on a western diet.
• it takes a lot more MK-4 supplementation than MK-7 to be detected in the blood
• MK-4 has a much shorter half life in the blood

• MK-4 is transported by LDL (low-density lipoproteins) and HDL (high-density lipoproteins).
• positioned on the outer layers
• off-loaded first
• distributed to kidneys, brain, heart, lungs and muscles
• MK-4 is most readily absorbed in organs and soft tissues.
• MK-7 is transported by LDL and VLDL (very low-density lipoproteins).
• positioned near the center
• off-loaded last
• distributed to the liver, where it is repackaged as VLDL's for delivery to bones
• MK-7 is most readily absorbed into bone.

• Studies with pregnant women have shown that:
• MK-4 passes through the placenta and on to the fetus
  • as evidenced by the presence of MK-4 found in the cord blood
• Mk-7 was NOT found in cord blood
• indicating that MK-7 can NOT pass through the placenta.
• Studies on human breast milk have shown that:
• MK-4 is the predominant form of Vitamin K2 found in human breast milk.
• Pregnant women, developing fetus and babies require MK-4 to meet their vitamin K2 needs.
• Studies , which correlated lowered fracture risk with Vitamin K2 consumption
  were conducted with MK-4 not MK-7.
• High dose MK-4 is the form of Vitamin K2 used in Japan as a prescription drug for osteoporosis.

I believe the primary reason is that promotors (of anything) tend to "talk their book".

MK-7 is substantially cheaper than MK-4, and typically more profitable.
Perhaps some folks need a narrative (other than greed) to support their agenda.

• The main cornerstone to the anti-MK-4 argument is that MK-4 has a much shorter plasma half-life than does MK-7. The implication being that, more frequent doses of MK-4 must be taken as compensation.

This is a bit of a fallacy.

Although its true that MK-7 can be detected in the blood for a longer time than MK-4 can, that's no reason to disparage MK-4.

On the contrary, Its not as if MK-4 just breaks downs and is gone forever. Rather, it dissipates from the blood rapidly, because it is "soaked up" so quickly and readily by the many organs and tissues that need it (much faster and in greater amounts than MK-7).

Keep in mind that even though the amount of MK-4 stored in the brain, pancreas, salivary glands, and arteries can't be measured, it is there . . . performing specific biological activities, and could even last longer in the body than MK-7 does.

• Another anti-MK-4 point is that MK-4 is synthetic, while MK-7 is natural.

Neither MK-4 nor MK-7 is truly natural. Both are "made from natural sources" like leaves, petals, and legumes. But both are highly processed, undergoing lots of fermentation, purification, extraction, and precipitation, so it's really not fair to call either of these ingredients "Natural".

• And another talking point is "There are no studies which prove MK-4 is superior to MK-7".

This is another fallacy.

While it is true that studies comparing MK-4 to MK-7 are sorely lacking . . . .
That's no reason to dismiss the assertion that MK-4 is superior to MK-7.

Most of MK-4 studies have been large scale clinical trials

Most MK-7 studies have focused on comparison with K1 (not MK-4).
and are sponsored by either the cheese or nato industry groups,

The bottom line is that Vitamin K2 research is still in its infancy and the truth is that we just don't know, what we don't know. All things considered however, based on the research conducted so far, one could reasonably argue that MK-4 is more important than MK-7 and NOT the other way around. But there is no reason to have to be in one camp or the other. We believe it is wise to be in both camps, which is why vK2, contains both MK-4 AND MK-7.

• Pregnant women and their fetuses are susceptible to Vitamin K2 deficiency.
• Some (but few) prenatal vitamins contain MK-7.
• I don't know of ANY prenatal vitamins that contain MK-4.
• This is potentially problematic:
• MK-4 can pass the blood placenta barrier, while MK-7 can not.
• Both "baby teeth" and "adult teeth" are formed in utero during weeks 5-12.
• Proper bone and dental development is impossible without adequate MK-4.
• Gut dysbiosis and statin use (both very common) contribute to Vitamin K2 deficiency.

• Effective dose
• Some researchers have suggested that 180 to 280 micrograms of MK-7 is enough.
• Other researchers have suggested that MK-4 may require a much higher dose
  
• MK-4 may be less bioavailable than MK-7.
• The body contains much more MK-4 than MK-7.
• 2012 Comparison of menaquinone-4 and menaquinone-7 bioavailability in healthy women
  Sato T, Schurgers LJ, Uenishi K. Nutri Journal. 2012;11:93.
  • This study compared the bioavailability of MK-4 and MK-7 in healthy volunteers in their serum (blood) levels.
  • They were given 420 mcg of MK-4 or MK-7 every morning along with breakfast.
  • MK-7 reached maximal serum level at 6 hours after intake and was detectable up to 48 hours after intake.
  • MK-4 was not detectable in the serum at any time point, even after 7 consecutive days of administration.
  • The researchers concluded that:
  • the current recommended dosage of MK-4 is too low,
    
  • a higher dose is required to improve the carboxylation of osteocalcin.

• Maximum dose
• There does not appear to be toxicity issues for either MK-4 or MK-7.
• MK-4
• 2014 Some Japanese studies have used 45 mg daily dosage without major side effects.
• MK-7
• 2017 US Pharmacopeial Convention safety evaluation of menaquinone-7
  Marles RJ, Roe AL, Oketch-Rabah HA., Nutr Rev. 2017 Jul 1;75(7):553-578.
• Bioactivity
• MK-4 and MK-7 exists in two isomer forms
• TRANS form is bioactive
• CIS form is NOT bioactive
• Vitamin K2 demand
• Anyone taking cholesterol-lowering statin drugs, has an increased demand for Vitamin K2
• 2015 Statins stimulate atherosclerosis and heart failure: pharmacological mechanisms
  Okuyama H, Langsjoen PH, Hamazaki T et al. Expert Rev Clin Pharmacol. 2015 Mar;8(2):189-99. doi: 10.1586/17512433.2015.1011125
• Anyone taking Vitamin D3, has an increased demand for Vitamin K2
• 2016 Calcimimetic and vitamin D analog use in hemodialyzed patients is associated with increased levels of vitamin K dependent proteins.
  Fusaro M, Giannini S, Gallieni M et al. Endocrine. 2016 Feb;51(2):333-41. doi: 10.1007/s12020-015-0673-z. Epub 2015 Jul 1.

We recommend taking one capsule of vK2 for every 5,000 iu of Vitamin D3