Vitamin K is a group of structurally similar vitamins required for carboxylation of certain
proteins in the human body, thereby activating them.
The classic example is activation of proteins in the blood clotting cascade in the liver
- vitamin K is used to add a carboxyl group to some of the clotting proteins, hence converting
them to their active form and allowing them to do their job.
But there are many other relatively recently-discovered proteins outside the liver that also require
this modification to become active.
There have been at least 10 more of these gla proteins discovered, involved in everything
from bone mineralisation to embryonic development.
Many of these proteins are active outside of the liver.
The reason I bring up location relative to the liver is that this is what makes the fundamental
difference between the different forms of vitamin K important - ability to make it past
the liver and into the general circulation.
Without getting into too much detail, the crux of the matter is that vitamin K1, or
phylloquinone, is relatively hydrophilic, whilst K2, or menaquinone, tends to have a
more hydrophobic tail, essentially allowing it to be transported and remain in the blood
longer, which in turn allows it to get to tissues outside of the liver.
But to complicate matters even more, vitamin K2 is again subdivided according to how long
this tail is, and the length of this tail further impacts it's ability to make it around
the body.
The chain length is designated by the number following 'MK' in vitamin K nomenclature.
For example, MK-4 is short making it relatively more hydrophilic like phylloquinone, whilst
MK-7 is longer making it more hydrophobic.
The most important forms for human health are MK-4 and MK-7.
MK-4 is the form most commonly used in animal tissues, thus animals, including humans, have
the ability to convert K1 into MK-4.
The concern is that this conversion is under-explored in humans, and may not fully meet demands,
especially considering that there may not be much K1 circulating in the first place
as we have discussed.
This is why it intuitively makes sense to take in the MK-4 form.
However, when this is studied, it appears that not much MK-4 makes it into the circulation
following acute or consecutive supplementation partly due to it's relatively hydrophilic
nature and possibly absorption issues, although a relatively low dose was used in this experiment.
And it follows that we need large doses of MK-4 to carboxylate extra-hepatic gla proteins,
which remember is the reason why we are interested in taking K2 it in the first place.
Enter MK-7.
MK-7 has a much longer half-life in the blood and appears to be better at carboxylating
these proteins.
Not only does it seem to be cleaved into MK-4 in the tissues, but MK-7 may actually be the
specific form needed in some tissues.
Conversely, MK-4 cannot be converted by humans to MK-7.
So it seems we get the best of both worlds from MK-7, and that is why it is the preferred
form for supplementation and the best-studied form.
But let's leave the discussion on supplements aside for now.
What are the dietary sources of vitamin K?
The most well-known source is dark green leafy vegetables and other plant foods, but what
you may not know is that they only provide K1.
As we have seen, animals, including humans convert K1 to MK-4, so this is the predominant
form found in non-fermented animal products.
But the only organisms capable of producing the long-chain menaquinones, MK-7 and upwards,
are fermenting bacteria.
That is why this is the predominant form found in fermented foods and produced in the large
intestine.
But as we will see, the bioavailability of these long-chain menaquinones produced by
gut bacteria is uncertain.
So given that dark green leafies provide only phylloquinone, animal products provide primarily
MK-4 and we don't know if we absorb much of the MK-7 produced in our gut, does that mean
we have to rely on fermented foods, of which really only nattō is a good source?
I am going to preface the following discussion answering that question by saying that this
whole area is not at all well-studied - in a situation analogous to choline which I discussed
in my last video, different forms of vitamin K are simply not a research priority or a
big public health concern, so we cannot answer these questions comprehensively due to the
lack of data.
As I mentioned earlier, animals, including humans, can convert phylloquinone to the MK-4
form of menaquinone in some tissues, but this conversion appears to be variable and perhaps
incomplete.
However, we must bear in mind that these proteins are still getting carboxylated to some degree
and performing their functions somehow, despite the fact that though almost no-one eats nattō
on a regular basis or supplements K2.
Likewise, taking anicoagulant drugs that interfere with vitamin K activity increase the risk
of calcification and fracture, so we know that the vitamin K most of us are getting
is doing it's job.
This is one of the reasons why nutrition authorities, most recently the European Food Safety Authority
in 2017, do not set specific dietary reference intakes for the different forms of vitamin
K.
The evidence simply isn't there to tell us that there is a need to get both forms in
for adequate carboxylation and health.
It's also why Cronometer does not have a seperate bar for K2.
That being said, K2 specifically does appear to possibly have a protective effect.
One prospective cohort study found quite an impressive significantly reduced risk of incident
heart disease and heart disease mortality when comparing the highest tertile of K2 intake
with the lowest, whilst a similar study found no such effect.
This is supported by cross-sectional data suggesting an association between higher K2
intake and less coronary calcification.
Similarly, K2 may have a role to play in supporting bone health, but again the findings are mixed.
Additionally, there are other emerging potential benefits that we are only just beginning to
explore.
This is no surprise, given the variety of gla proteins in different tissues.
Given that there are potential benefits, the next area that must be explored is risks and
safety profile to help us come to a decision on whether or not to supplement.
K2 MK-7 is widely-regarded to be safe when taken at recommended doses as a dietary supplement.
Because of it's good safety profile and potential benefit, and following exactly the rationale
I have outlined in this video, I take vitamin K2 myself.
However, because this potential benefit is small, especially compared with some of the
non-negotiable supplements I recommend like vitamins B12 and D, in addition to the fact
that the guidelines do not give recommendations for K2 specifically based on the best-available
evidence, I do not recommend the supplement to everyone.
If, after following my rationale outlined in this video and of course based on your
own research, and if the supplement is within your means, then feel assured that at worst
the supplement is not going to do any harm, and at best it might actually give you some
benefit if you do decide to take it.
Notice as well that I said "supplement", not source from food, with one exception.
There is only one good food source of MK-7 and that is nattō, but by all accounts this
fermented soybean food is not very acceptable to Western palates.
Other sources of K2 invariably contain relatively little K2 and little to no MK-7 specifically.
And even if they did, remember the whole point of why we want to take K2 is mainly to reduce
our cardiovascular risk.
Non-nattō sources of K2 are almost all fatty animal products which are now undeniably connected
with cardiovascular disease.
Indeed, MK-7 supplements are usually derived from nattō bacteria.
So how about dose?
Because of everything we have discussed so far in this video in addition to the fact
that there is no good test for vitamin K status, it is difficult to determine appropriate dosage,
but the general consensus is that most of the benefit can be obtained from the first
100 mcg of MK-7.
As with any supplement, make sure you discuss starting K2 with your doctor if you do decide
you want take it because it can interfere with vitamin K antagonist drugs and theoretically
could play a role in destabilising pre-existing atherosclerotic plaques.
If you want my personal opinion, I think there are undiscovered mechanisms by which we can
get the appropriate form of vitamin K to the relevant proteins.
My best guess is that the currently unknown rate of absorption of MK-7 from the bacteria
that produce it in our large intestine is sufficient to meet our needs in the presence
of a healthy intestinal microbiome and a good intake of K1 for conversion and to spare requirement
for K2.
I also wonder that because not everyone fulfills these criteria, if some of the recent conflicting
stuff we have seen on vitamin D is down to this insufficiency of vitamin K along with
high doses of vitamin D, but there is no way of knowing if there is a connection here at
present.
Either way, there are a number of randomised controlled trials currently underway pitting
MK-7 against coronary artery calcification amongst other things, with results from this
one due in October of this year, so hopefully they will bring us one step closer to knowing
if vitamin K2 supplements are worth taking!
In summary, vitamin K2 isn't one of those make-or-break supplements like B12.
However, there may be some potential benefit and this area is currently the subject of
investigation.
For now, the best you can do is to make up your own mind based on your own research and
see if it's worth it for yourself, whilst resting assured that the supplement is safe.
That's it guys, hope you learned a little something about vitamin K2!
Give us an old thumbs up there if you found the video informative and share it with anyone
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I'll be back to ye soon with another nutrient of concern, so make sure you subscribe if
you haven't already so you don't miss that one!
Talk to ye soon.
Sláinte!