K2 Mk4 Or Mk7?

[Momado965]

So which of the two forms hel with vitamin d3 and calcium deposting?

The video below specifically claims the artery protective benefits are from mk7

 

[paymanz]

Maybe one of them being a bit more potent than other one but it's not a big difference.

They say mk7 is more potent but mk4 also has those benefits for calcium metabolism too.

I think mk7 is more bioavailable and has a longer half life.

Reversed Warfarin Induced Arterial Calcification By Vitamin K Supplement And K1 As Effective As K2

 

[ecstatichamster]

never got any good results from MK7.

 

[haidut]

The large scale clinical trials are mostly with MK-4. The Japanese also have access to MK-7 and can produce it a lot more cheaply than MK-4 by using nato. Yet, they still went with MK-4. Most of the MK-7 trials so far are sponsored by either cheese or nato industry groups. There is notable lack of studies comparing MK-7 and MK-4. Probably because MK-4 will be found superior or at least as good as MK-7. The trials so far on MK-7 focus on comparisons with K1, which we know is inferior to the menaquinones. MK-4 is also the form used by the humans for functions such as electron transport carrier and co-factor for the carboxylation of osteocalcin. MK-7 is at best a surrogate for MK-4.

 

[Momado965]

The large scale clinical trials are mostly with MK-4. The Japanese also have access to MK-7 and can produce it a lot more cheaply than MK-4 by using nato. Yet, they still went with MK-4. Most of the MK-7 trials so far are sponsored by either cheese or nato industry groups. There is notable lack of studies comparing MK-7 and MK-4. Probably because MK-4 will be found superior or at least as good as MK-7. The trials so far on MK-7 focus on comparisons with K1, which we know is inferior to the menaquinones. MK-4 is also the form used by the humans for functions such as electron transport carrier and co-factor for the carboxylation of osteocalcin. MK-7 is at best a surrogate for MK-4.

Your answer sufficed, Haidut. Thank you big time!

 

[LucH]

MK-4 is also the form used by the humans for functions such as electron transport carrier and co-factor for the carboxylation of osteocalcin. MK-7 is at best a surrogate for MK-4.

Well seen
MK-4 has effects on gene expression in bone tissue that MK-7 doesn't have.
"The investigators found that MK-4 strongly activates transcription of two specific genes in osteoblast cells. Osteoblasts are cells that create bone tissue. The genes are GDF15 and STC2 and they're involved in bone and cartilage formation. They tested K1 and MK-7, and in contrast to MK-4, they did not activate transcription of the genes in the slightest. This shows that MK-4 has effects on gene expression in bone tissue that MK-7 doesn't have."
MK-7 has also less interaction with enzymes that would bring it into the cells (due to a longer side-chain, more lipophile)
Source: Mk4 is preferably used by body
“Vitamin K2 induces phosphorylation of protein kinase A and expression of novel target genes in osteoblastic cells”
T Ichikawa1, K Horie-Inoue1, K Ikeda1, B Blumberg2 and S Inoue1,3 1


I would not recommend taking more than 2 mg / day, given the fact that the menaquinones (K2 family) are broken down into menadiones, which can be "toxic" If repeated.
http://ajplung.physiology.org/content/ajplung/262/5/L637.full.pdf

http://www.ncbi.nlm.nih.gov/pubmed/1990978
=> Stress bringing depletion of Glutathion
NB 2 mg = 2000 mcg.

 

[haidut]

Well seen
MK-4 has effects on gene expression in bone tissue that MK-7 doesn't have.
"The investigators found that MK-4 strongly activates transcription of two specific genes in osteoblast cells. Osteoblasts are cells that create bone tissue. The genes are GDF15 and STC2 and they're involved in bone and cartilage formation. They tested K1 and MK-7, and in contrast to MK-4, they did not activate transcription of the genes in the slightest. This shows that MK-4 has effects on gene expression in bone tissue that MK-7 doesn't have."
MK-7 has also less interaction with enzymes that would bring it into the cells (due to a longer side-chain, more lipophile)
Source: Mk4 is preferably used by body
“Vitamin K2 induces phosphorylation of protein kinase A and expression of novel target genes in osteoblastic cells”
T Ichikawa1, K Horie-Inoue1, K Ikeda1, B Blumberg2 and S Inoue1,3 1


I would not recommend taking more than 2 mg / day, given the fact that the menaquinones (K2 family) are broken down into menadiones, which can be "toxic" If repeated.
http://ajplung.physiology.org/content/ajplung/262/5/L637.full.pdf

http://www.ncbi.nlm.nih.gov/pubmed/1990978
=> Stress bringing depletion of Glutathion
NB 2 mg = 2000 mcg.

Great, thanks. I knew that K2 gets metabolized into K3 (menadione) and the latter is toxic, but I thought studies looked at this metabolic pathway and did not find significant elevations of K3 after K2 ingestion? Maybe K3 is rapidly eliminated as a toxic substance...
Also, how did you come up with the 2mg cut off dose? Does it mean that more than 2mg K2 at a time will lead to toxic levels of K3? Or did the study find that more than 2mg K3 is toxic. Finally, I think a relatively small proportion of K2 gets metabolized into K3. The majority of the K2 stays as such and gets accumulated in liver, brain, spleen, pancreas, and bones. Do you have any other data on pharmacology and metabolism of K2 into K3?

 

[Momado965]

Well seen
MK-4 has effects on gene expression in bone tissue that MK-7 doesn't have.
"The investigators found that MK-4 strongly activates transcription of two specific genes in osteoblast cells. Osteoblasts are cells that create bone tissue. The genes are GDF15 and STC2 and they're involved in bone and cartilage formation. They tested K1 and MK-7, and in contrast to MK-4, they did not activate transcription of the genes in the slightest. This shows that MK-4 has effects on gene expression in bone tissue that MK-7 doesn't have."
MK-7 has also less interaction with enzymes that would bring it into the cells (due to a longer side-chain, more lipophile)
Source: Mk4 is preferably used by body
“Vitamin K2 induces phosphorylation of protein kinase A and expression of novel target genes in osteoblastic cells”
T Ichikawa1, K Horie-Inoue1, K Ikeda1, B Blumberg2 and S Inoue1,3 1


I would not recommend taking more than 2 mg / day, given the fact that the menaquinones (K2 family) are broken down into menadiones, which can be "toxic" If repeated.
http://ajplung.physiology.org/content/ajplung/262/5/L637.full.pdf

http://www.ncbi.nlm.nih.gov/pubmed/1990978
=> Stress bringing depletion of Glutathion
NB 2 mg = 2000 mcg.

Thank you for the gathered info, Luch. Do you think a dose of 45mg of mk4 spread throughout is toxic? Many ppl do take doses in that range some even are on the lower side 15mg daily.

 

[LucH]

Does it mean that more than 2mg K2 at a time will lead to toxic levels of K3?

Well, we don't know exactly. This is a supposed byside effect. I explain.

Conversion of excess menaquinones in menadiones
We know menadione is a metabolite of oral vitamin K supplement.
Phylloquinone (K1) is converted into menaquinone-4 and accumulates in extrahepatic tissues. Neither the route nor the function of the conversion is totally known. One supposed metabolic route is the conversion of 5 – 25 % of menadione from phylloquinone by catabolic activity. 10 – 15 % is most likely converted. But this is aleatory (due to intestinal absorption) and not equally distributed. We can only measure the presence of menadione in urine and make deductions when excreted. (1)
When taking excess menadiones, through conversion / excretion it would be quite advisable to take some NAC to get enough selenium to neutralize ROS. Adaptive response. (2) Menadione generates ROS through redox cycling, and high concentrations trigger cell death. If lack of glutathione. (3 – 4)
Menadione in excess clearly affects the mitochondrial function. (5)
However there is no reported health risk when taking K2. Excess K2 is excreted through urine and feces (through bile). No direct adverse effect doesn’t mean there is no impact on energy level. This is a personal comment. It depends on the way the body neutralizes an excess oral supplement.
Mind excess alpha-tocopherols too (vitamin E) because it may interfere with synthesis of K2. (6- 7) Also if you take phytonutrients as AINS (curcumine or aspirin) because it affects cytochrome P450 (detox pathway). You need a recovery period between 2 cures.
1. https://www.researchgate.net/publication/7305589_Menadione_is_a_metabolite_of_oral_vitamin_K
2. http://www.jbc.org/content/281/52/40485.full.pdf
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3005834/
Oxidative Stress-Induced Apoptosis by Menadione at high concentration.
3. https://www.ncbi.nlm.nih.gov/pubmed/20937380 +
4. http://www.sciencedirect.com/science/article/pii/S1521661601951290
5. http://jcs.biologists.org/content/106/1/309
6. http://health.oregonstate.edu/biblio/vitamin-e-decreases-extra-hepatic-menaquinone-4-concentrations-rats-fed-menadione-or
7. http://www.pubpdf.com/pub/22707266/Vitamin-E-decreases-extra-hepatic-menaquinone-4-concentrations-in-rats-fed-menadione-or-phylloquinon
α-Toco may interfere with the side chain removal of phylloquinone (PK) to form menadione (MN) as an intermediate for synthesis of tissue-specific menaquinone-4 (MK-4).

 

[LucH]

Do you think a dose of 45mg of mk4 spread throughout is toxic?

Toxic, no.
K1= 45 mcg.
Enough to improve the level of artery calcification and cardiac mortality. It depends on the interaction between A D K vitamins.
K2 type MK4: 45 mg (45.000 mcg).
Recommended to decarboxylate the Osteocalcin level.
K2 type MK7: 240 mcg for diabetics and obese people. Level recommended in the prevention of atherosclerosis, diabetes, osteoporosis, obesity, etc.
From « Dosage optimum » on this link (in French):
http://mirzoune-ciboulette.forumactif.org/t706-vitamine-k2-achat-exemples-de-produits#6433

 

[haidut]

Well, we don't know exactly. This is a supposed byside effect. I explain.

Conversion of excess menaquinones in menadiones
We know menadione is a metabolite of oral vitamin K supplement.
Phylloquinone (K1) is converted into menaquinone-4 and accumulates in extrahepatic tissues. Neither the route nor the function of the conversion is totally known. One supposed metabolic route is the conversion of 5 – 25 % of menadione from phylloquinone by catabolic activity. 10 – 15 % is most likely converted. But this is aleatory (due to intestinal absorption) and not equally distributed. We can only measure the presence of menadione in urine and make deductions when excreted. (1)
When taking excess menadiones, through conversion / excretion it would be quite advisable to take some NAC to get enough selenium to neutralize ROS. Adaptive response. (2) Menadione generates ROS through redox cycling, and high concentrations trigger cell death. If lack of glutathione. (3 – 4)
Menadione in excess clearly affects the mitochondrial function. (5)
However there is no reported health risk when taking K2. Excess K2 is excreted through urine and feces (through bile). No direct adverse effect doesn’t mean there is no impact on energy level. This is a personal comment. It depends on the way the body neutralizes an excess oral supplement.
Mind excess alpha-tocopherols too (vitamin E) because it may interfere with synthesis of K2. (6- 7) Also if you take phytonutrients as AINS (curcumine or aspirin) because it affects cytochrome P450 (detox pathway). You need a recovery period between 2 cures.
1. https://www.researchgate.net/publication/7305589_Menadione_is_a_metabolite_of_oral_vitamin_K
2. http://www.jbc.org/content/281/52/40485.full.pdf
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3005834/
Oxidative Stress-Induced Apoptosis by Menadione at high concentration.
3. https://www.ncbi.nlm.nih.gov/pubmed/20937380 +
4. http://www.sciencedirect.com/science/article/pii/S1521661601951290
5. http://jcs.biologists.org/content/106/1/309
6. http://health.oregonstate.edu/biblio/vitamin-e-decreases-extra-hepatic-menaquinone-4-concentrations-rats-fed-menadione-or
7. http://www.pubpdf.com/pub/22707266/Vitamin-E-decreases-extra-hepatic-menaquinone-4-concentrations-in-rats-fed-menadione-or-phylloquinon
α-Toco may interfere with the side chain removal of phylloquinone (PK) to form menadione (MN) as an intermediate for synthesis of tissue-specific menaquinone-4 (MK-4).

Great, thanks for the explanation and references. So, it seems that in conditions characterized by reductive stress (cancer, diabetes, etc) this overproduction of ROS may be desirable as the tumors surround themselves with NAC and reduced glutathione to protect themselves from ROS. This is how William Koch explained the activity of emodin, lapachone and other quinones against cancer back in the 1920s. But in a healthier person, on should be careful not to ingest too much K2 as it can lead to too much oxidative stress. I think selenium is a much safer option then NAC. The cysteine has a lot of bad effects on the organism. Taking glycine will combine with NAC in the body to form glutathione. Since we all ingest decent amount of NAC with food, it seems like selenium and glycine would be safer options of raising glutathione then ingesting extra NAC. What's your thought on selenium and/or glycine vs. NAC supplementation?

 

[paymanz]

α-Toco may interfere with the side chain removal of phylloquinone (PK) to form menadione (MN) as an intermediate for synthesis of tissue-specific menaquinone-4 (MK-4).

that means k3 is a byproduct of k1 to k2 conversion?

you didnt meant to say alpha tocopherol inhibit its conversion ,right?

K1= 45 mcg.
Enough to improve the level of artery calcification and cardiac mortality. It depends on the interaction between A D K vitamins.

i know some people dont have even that small dose of k1 in their diet and can greatly benefit from only 45 mcg but higher doses can deliver even more of that artery protection. it have been shown 1,000 mcg of k1 is enough to maximally carboxylate the osteocalcin.

Another reference, Vitamin K Supplementation in Postmenopausal Women with Osteopenia (ECKO Trial): A Randomized Controlled Trial

Another one that compares 1mg k1 vs 45mg k2 mk4
Vitamin K Treatment Reduces Undercarboxylated Osteocalcin but Does Not Alter Bone Turnover, Density, or Geometry in Healthy Postmenopausal North American Women

Here k1 vs k2 mk4 similar effects on matrix gla protein carboxylation, another vitamin k dependant protein.
Matrix Gla Protein and Alkaline Phosphatase Are Differently Modulated in Human Dermal Fibroblasts from PXE Patients and Controls - ScienceDirect

 

[LucH]

I think selenium is a much safer option then NAC. The cysteine has a lot of bad effects on the organism.

Yes, cysteine could depress thyroid function in case of insufficient iodine.

Excerpt from RP’s article on Gelatin:
The amino acids cysteine and tryptophan, released in large quantities during stress, have anti-metabolic (thyroid-suppressing) and, eventually, toxic effects.
Both tryptophan and cysteine inhibit thyroid function and mitochondrial energy production, and have other effects that decrease the ability to withstand stress. Tryptophan is the precursor to serotonin, which causes inflammation, immune-depression, and generally the same changes seen in aging. Histidine is another amino acid precursor to a mediator of inflammation, histamine; would the restriction of histidine in the diet have a longevity promoting effect, too?
(…)
A generous supply of glycine/gelatin, against a balanced background of amino acids, has a great variety of anti-stress actions. Glycine is recognized as an “inhibitory” neurotransmitter, and promotes natural sleep. Used as a supplement, it has helped to promote recovery from strokes and seizures, and to improve learning and memory.
Gelatin, stress, longevity

To prevent inhibitory effect from cysteine onto thyroid some people would say we need to eat seafood (fish and shrimps, but not algae because too high in iodine). So a moderate amount. But it’s not a good idea to practise so. Not a good profile of amino acids, except if we add some bone broth or collagen supplement.
“The iodide oxidation inhibitory activity of cysteine, methionine and tryptophan was reversed by increasing iodide concentrations from 12 to 18 mM.
(…)
The inhibitory substances might interfere with the enzyme activity by competing with its normal substrates for their binding sites, binding to the free substrates or reducing their oxidized form.”
http://www.ncbi.nlm.nih.gov/pubmed/10719389
I repeat: overdosing on iodine is not a good idea. “A dosage of 150 mcg is safe according to RP.
100~200 mug/l is the normal range but we’d better reduce this fork. If we are too close from the upper limit, it could indicate a too high level of pufa in our body since pufa contains more iodine.
So iodine could be a good or a bad guy ..


Haidut asked:
“What's your thought on selenium and/or glycine vs. NAC supplementation?”
=> Both are useful.
NAC is not a good idea as recurrent supplement if you suffer from lithiasis, thyroid or if you don’t balance with glycine. Interesting when in crisis with asthma or bronchitis in order to fluidize the mucus.
I prefer selenium. 2 or 3 Brazil nuts twice a week for most people is sufficient. But if you want to neutralize mercury when dieting (lipolysis), you’d better add some extra selenium. Seleniomethionine is easier to find, more bioavailable (60 %) than selenite (40 %).
More support for selenomethionine bioavailability - Sabinsa Corporation
American Journal of Clinical Nutrition (Vol. 81, pp. 829-834, April 2005).

Selenomethionine was more bioavailable than selenium selenite in a selenium-deficient Chinese population.
https://www.lef.org/magazine/mag2012/ss2012_Selenium-Protect-Against-Cancer_01.htm
Sodium selenite enhances the repair of damaged DNA segments, reducing the risk of new cancer. Sodium selenite increases the likelihood that abnormal cancer cells will be destroyed.

For me 50 to 100 mcg Se is well. 200 maxi, except when detoxifying (400 mcg in attack after 2 or 3 days)
Too much selenium could be counterproductive and acts as oxidant.
Btw, when I eat fish, I take 1 caps chlorella, only one caps; no more.

 

[LucH]

Paymanz said:
“you didnt meant to say alpha tocopherol inhibit its conversion ,right?”
=> Tocopherols neutralize oxidant molecules. If excess menaquinone leaves quinones, if menadione generates ROS, yes, alpha tocopherols would serve as firemen. Thus tocopherols could inhibit K2 when taken at the same time. Only a supposition but it’s logical.

 

[HealthisWealth]

Hi i saw this k2 in the supplement store

Ingredients
K2 75mcg (mixed mk4 through mk10)
GLA 250mg (Gamma-glutamyl carboxylase = choline and glutamic acid)

is this good mk4 through mk10 and is choline and glutamic acid bad?

 

[paymanz]

75mcg is very low dose for a supplement.

 

[HealthisWealth]

75mcg is very low dose for a supplement.

Yes but this only the available in my country.

In few months a relative from america will visit my country. Among this which is the best and ease of use. thorne k2, life extension, healtnatura, complimentary prescription. Are drops for skin only or can be use orally?

What can you say about the other ingredients (GLA 250mg Gamma-glutamyl carboxylase = choline and glutamic acid)

Im using vitamin D3 so i need to balance it with K2

 

[paymanz]

if i were you i would wait that few months to find a good supplement.

now if you read my above comment before you post you see im a k1 fan , in my opinion if you eat some veggies high in vitamin k level you can benefit more(compared to the supplement you mentioned), if you get like 400-500 mcg k1 from veggies which is not hard to get.

mk4 through mk10 is good profile but dosage is low.however that GLA part of supplement maybe make the 75mcg more usable, i never thought you can supplement GLA, i think that can improve anti bleeding and bone building and artery protecting effect of vitamin k. maybe thats good for some people with low GLA levels(osteocalcin is one of those GLA proteins).

 

[HealthisWealth]

@paymanz

So i need to up my green leafy vegetable consumption. Do i need to large servings to achieve good amount of K1 to balance the D3? How about K1 in supplement is this ok?

Does GLA really mean Gamma-glutamyl carboxylase not gamma linolenic acid?

 

[paymanz]

@paymanz

So i need to up my green leafy vegetable consumption. Do i need to large servings to achieve good amount of K1 to balance the D3? How about K1 in supplement is this ok?

Does GLA really mean Gamma-glutamyl carboxylase not gamma linolenic acid?

havent it mentioned if its gamma linolenic acid or Gamma-glutamyl carboxylase? if so then i think its that GLA from borage oil because as i said i never heard they supplement GLA proteins.i think ray is no good with GLA(oil).

yes just some veggies , kale ,lettuce , spinach , parsley are good source these can be cooked which is good for vitamin k bioavailability too. and some fat with it improve absorption.vitamin k is sensitive to air , so dried veggies is not good option.

i would not do too much of them because their high in beta caroten too ,but as i said 400-500 mcg even up to 1000 mcg probably is attainable without caroten excess, some of them are lower on caroten, you can check in nutritiondata.com.

btw vitamin A(retinol) is very important to have with vitamin D.also its good to check your levels , i think more than 40 ng is not a good thing.