Vitamin K is a closely related group of molecules. The main division is into K1 (Phytomenadione), K2 (Menaquinone) and K3 (Menadione). The first two types occur naturally in food and the third is created synthetically and used in animal feed.
Originally K was identified and named by Henrik Carl Peter Dam (1895-1976) and Edward Adelbert Doisy (1893-1986) because it assisted in the coagulation of blood, but another function relates to handling the calcium balance in blood. It was perhaps second noticed for its benefits for dental health.
In Particular K2 has been identified as being good at ensuring that calcium is built into bones and not into soft tissue (be that arterial calficiation or elsewhere). There is a debate as to whether K2-Mk4 or K2-Mk7 is more effective. The different types of K2 are named depending upon the number of molecular parts called isoprene residues attached to the original vitamin K structure. Unsurprisingly MK4 has 4 and MK7 has 7. There are quite a few different versions of K2, but only those of 4 and 7 are commonly found.
MK-7 has an effect at lower doses (it can be eaten from Natto) it is also argued that MK-7 particularly reduces the calcification of arteries, but it is also argued that MK-4 when it deposits calcium in bones does so in a way which makes the bones stronger. MK-7 also causes a problem for some people (such as me) in that it harms sleep maintenance so you wake up in the middle of the night. When reading articles about this be careful to notice that doses of MK-7 are often quoted in micrograms (mcg or μg) and doses of MK-4 quoted in doses of milligrams (mg). It has been shown that Mice convert K1 into K2 MK-7. There is therefore a good chance that other mammals do this as well. An experiment on rats found that K1 converted to K3 and thence to K2
https://www.sciencedirect.com/science/article/pii/S0085253815302854
https://www.frontiersin.org/articles/10.3389/fcvm.2019.00006/full
Further on the D/K issue
This report found MK7 reduced arterial stiffness, but extra MK4 did not unless people were deficient This again encourages the use of MK4 to reduce arterial stiffness
If taking Mk4 then at least 600mcg is needed MK7 does cause some people sleep problems.
There are links which provide some detail of what different types of vitamin K can be found in various foods particularly such as cheese. However, I would assume that different sorts of cheese have different proportions of different K2 varieties hence you cannot necessarily rely on that. Furthermore it is not just MK-4 and MK-7 that is found in food, but also the other types and they also have effects (although not as well studied).
Hence I am not going to come to any firm conclusion on this issue although I would say firmly that it is worth having some K2, whether taking K1 is sufficient to create K2 or not I cannot say definitively no. However, I would also not rely on that. Hence K2 does seem to warrant some action. In reading other documents it is clear that there are contradictions between documentation which may arise from confusion between MK-4 and MK-7. What I would say is that if you are trying both MK4 and MK7 it is best to take them separately rather than in a combined dose so that you can separate out the effects.
Sleep and Energy
There is quite a bit of research that indicates that K2 (particularly MK-7) can act as an assistance to the generation of energy by mitochondria in being available for electron transport. There has also been an RCT that says Oral Consumption of Vitamin K2 for 8 Weeks Associated With Increased Maximal Cardiac Output During Exercise. My own experience is that MK-7 causes me sleep problems immediately on the day I take it. MK-4 causes similar problems admittedly with a higher dose and after a couple of days. I think it also pushes up my resting heart rate (by about 5-10bpm), but I intend at some stage to do some experimentation to track that reliably. I have, however, done further experimentation with mk4 and mk7. I experimented taking about 15mg of mk4 and 5 drops of mk7 (approx 1mg in total). This initially caused serious sleep difficulties with waking at about 2am, but I found that if I got drunk the mixture of alcohol and mk balanced each other out and I slept ok, but got a hangover. After about a week, however, sleep without alcohol became more reliable, but fitbit could not reliably measure sleep. Most importantly for me it went a long way towards fixing a problem with one of my teeth that I had a material problem with. This experiment is continuing, however.
Menaquinones from Food There are quite a few ways of getting menaquninones from food. Generally some form of fermentation needs to go on to get a good level of MK. Some cheeses are good for this, but the sort of processed cheese from milk from cows that are not grass fed or in the sun themselves tends to be that good. Best really that I give a few links. The research on this tends to conflict in the detail and each individual foodstuff could vary without it being obvious. It would be good if producers told us what levels of menaquinone there was for each MK number, but they generally don't. This produces less than a supplement, but that may help if you have a problem from being kept awake by the supplements.
Menaquinone Content of Cheese
Quantitative measurement of vitamin K2 (menaquinones) in various fermented dairy products using a reliable high-performance liquid chromatography method
Menaquinones, Bacteria, and Foods: Vitamin K2 in the Diet
Vitamin K2 Rich Food Products
Look for foods with the longer chains (7-13) as well as 4.
Fermented foods Note with these that they have MK other than 4 and 7. Mk-9 is available as a supplement, but not other MK other than 4 and 7. Determination of vitamin K composition of fermented food Menaquinones, bacteria, and the food supply: the relevance of dairy and fermented food products to vitamin K requirements
There in fact is now an MK9 supplement available. I have not managed to get anything to say about it as I have not yet experimented with taking MK9 and not the other K2 supplements. I do think, however, that it is best to take MKn supplements in the morning. When I took them in the evening with dinner I think it caused quite a high heart rate at night. I will test this a bit,but because it disrupted my sleep I am not prioritising testing it.
Some more links This is a page arguing for MK-4 only Tissue-specific utilization of menaquinone-4 results in the prevention of arterial calcification in warfarin-treated rats
Vitamin K2 (Menaquinone-7) Reverses Age-Related Structural and Cognitive Deterioration in Naturally Aging Rats
The health benefits of vitamin K
K supplements comparison Menaquinone-4 accelerates calcification of human aortic valve interstitial cells in high-phosphate medium through PXR - a counter argument
Someone else's list of research
The Ultimate Vitamin K2 Resource
Reddit: Vitamin K2 - MK4 vs MK7 Latest
Low-dose vitamin K2 (MK-4) supplementation for 12 months improves bone metabolism and prevents forearm bone loss in postmenopausal Japanese women
Pharmacokinetics of Menaquinone-7 (Vitamin K2) in Healthy Volunteers
Linus Pauling Institute on Vitamin K
good K review More links for sorting: Vitamin K2 Modulates Mitochondrial Dysfunction Induced by 6-Hydroxydopamine in SH-SY5Y Cells via Mitochondrial Quality-Control Loop
The Relationships Between Vitamin K and Cognition: A Review of Current Evidence
link
link
Vitamin K2 is a mitochondrial electron carrier that rescues pink1 deficiency - refers to MK-4 not MK-7 although says MK-n
Menaquinone (Vitamin K2) Biosynthesis: Localization and Characterization of the menA Gene fromEscherichia coli
link
link
link
link
link
link
link
link
link
link
link
5/7/553/3859571 https://a 10mcg MK-7 can affect Vitamin K agonists https://a5/7/553/3859571 https://adosage review MK4
Activator X MK-4
John E Whitcomb, MD - good presentation
https://aon dosing
5/7/553/3859571 Vitamine k2 and the “calcium paradox” in dental prophylaxy
A really good article about calcification of the pineal gland Please note that I am not associated with any of these links nor do I endorse anything that I link to. Some links contain material that I think is wrong.
https://www.frontiersin.org/articles/10.3389/fcvm.2019.00006/full
Further on the D/K issue
This report found MK7 reduced arterial stiffness, but extra MK4 did not unless people were deficient This again encourages the use of MK4 to reduce arterial stiffness
If taking Mk4 then at least 600mcg is needed MK7 does cause some people sleep problems.
The MK-4 vs MK-7 debate
What is clear is that it is worth having some Vitamin K. Although it is argued by some that there has not been a defined maximum Vitamin K, I can confirm through personal experience that not very much MK-7 can cause some difficulties with sleep. I would not, however, say that the evidence comes firmly down on either MK-4 or MK-7 or even taking both as supplements.There are links which provide some detail of what different types of vitamin K can be found in various foods particularly such as cheese. However, I would assume that different sorts of cheese have different proportions of different K2 varieties hence you cannot necessarily rely on that. Furthermore it is not just MK-4 and MK-7 that is found in food, but also the other types and they also have effects (although not as well studied).
Hence I am not going to come to any firm conclusion on this issue although I would say firmly that it is worth having some K2, whether taking K1 is sufficient to create K2 or not I cannot say definitively no. However, I would also not rely on that. Hence K2 does seem to warrant some action. In reading other documents it is clear that there are contradictions between documentation which may arise from confusion between MK-4 and MK-7. What I would say is that if you are trying both MK4 and MK7 it is best to take them separately rather than in a combined dose so that you can separate out the effects.
Sleep and Energy
There is quite a bit of research that indicates that K2 (particularly MK-7) can act as an assistance to the generation of energy by mitochondria in being available for electron transport. There has also been an RCT that says Oral Consumption of Vitamin K2 for 8 Weeks Associated With Increased Maximal Cardiac Output During Exercise. My own experience is that MK-7 causes me sleep problems immediately on the day I take it. MK-4 causes similar problems admittedly with a higher dose and after a couple of days. I think it also pushes up my resting heart rate (by about 5-10bpm), but I intend at some stage to do some experimentation to track that reliably. I have, however, done further experimentation with mk4 and mk7. I experimented taking about 15mg of mk4 and 5 drops of mk7 (approx 1mg in total). This initially caused serious sleep difficulties with waking at about 2am, but I found that if I got drunk the mixture of alcohol and mk balanced each other out and I slept ok, but got a hangover. After about a week, however, sleep without alcohol became more reliable, but fitbit could not reliably measure sleep. Most importantly for me it went a long way towards fixing a problem with one of my teeth that I had a material problem with. This experiment is continuing, however.
Menaquinones from Food There are quite a few ways of getting menaquninones from food. Generally some form of fermentation needs to go on to get a good level of MK. Some cheeses are good for this, but the sort of processed cheese from milk from cows that are not grass fed or in the sun themselves tends to be that good. Best really that I give a few links. The research on this tends to conflict in the detail and each individual foodstuff could vary without it being obvious. It would be good if producers told us what levels of menaquinone there was for each MK number, but they generally don't. This produces less than a supplement, but that may help if you have a problem from being kept awake by the supplements.
Menaquinone Content of Cheese
Quantitative measurement of vitamin K2 (menaquinones) in various fermented dairy products using a reliable high-performance liquid chromatography method
Menaquinones, Bacteria, and Foods: Vitamin K2 in the Diet
Vitamin K2 Rich Food Products
Look for foods with the longer chains (7-13) as well as 4.
Fermented foods Note with these that they have MK other than 4 and 7. Mk-9 is available as a supplement, but not other MK other than 4 and 7. Determination of vitamin K composition of fermented food Menaquinones, bacteria, and the food supply: the relevance of dairy and fermented food products to vitamin K requirements
There in fact is now an MK9 supplement available. I have not managed to get anything to say about it as I have not yet experimented with taking MK9 and not the other K2 supplements. I do think, however, that it is best to take MKn supplements in the morning. When I took them in the evening with dinner I think it caused quite a high heart rate at night. I will test this a bit,but because it disrupted my sleep I am not prioritising testing it.
Some more links This is a page arguing for MK-4 only Tissue-specific utilization of menaquinone-4 results in the prevention of arterial calcification in warfarin-treated rats
Vitamin K2 (Menaquinone-7) Reverses Age-Related Structural and Cognitive Deterioration in Naturally Aging Rats
The health benefits of vitamin K
K supplements comparison Menaquinone-4 accelerates calcification of human aortic valve interstitial cells in high-phosphate medium through PXR - a counter argument
Someone else's list of research
The Ultimate Vitamin K2 Resource
Reddit: Vitamin K2 - MK4 vs MK7 Latest
Low-dose vitamin K2 (MK-4) supplementation for 12 months improves bone metabolism and prevents forearm bone loss in postmenopausal Japanese women
Pharmacokinetics of Menaquinone-7 (Vitamin K2) in Healthy Volunteers
Linus Pauling Institute on Vitamin K
good K review More links for sorting: Vitamin K2 Modulates Mitochondrial Dysfunction Induced by 6-Hydroxydopamine in SH-SY5Y Cells via Mitochondrial Quality-Control Loop
The Relationships Between Vitamin K and Cognition: A Review of Current Evidence
link
link
Vitamin K2 is a mitochondrial electron carrier that rescues pink1 deficiency - refers to MK-4 not MK-7 although says MK-n
Menaquinone (Vitamin K2) Biosynthesis: Localization and Characterization of the menA Gene fromEscherichia coli
link
link
link
link
link
link
link
link
link
link
link
5/7/553/3859571 https://a 10mcg MK-7 can affect Vitamin K agonists https://a5/7/553/3859571 https://adosage review MK4
Activator X MK-4
John E Whitcomb, MD - good presentation
https://aon dosing
5/7/553/3859571 Vitamine k2 and the “calcium paradox” in dental prophylaxy
A really good article about calcification of the pineal gland Please note that I am not associated with any of these links nor do I endorse anything that I link to. Some links contain material that I think is wrong.
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