K2 Mk4 Or Mk7?

[LucH]

never got any good results from MK7.

Degradation of vitamin K2 Mk7
Vitamin K2 MK-7 classic degrades very quickly (storage), in just a few months. (24) The difference in stability between the simple vitamin K2 MK-7 and the microencapsulated (or liposomal) form is very significant. The purity of the molecule probably plays a role at this level. (25-26) After 3 months, K2 MK7 only has 30% of its integrity / efficiency, 1% after 12 months. (24)
The manufacturer should indicate the degree of purity of the molecule (> 99%), if not distrust, giving details of the manufacturing level (with a quality label, to indicate compliance with a manufacturing procedure, for example) .
24) J. Venesson – Vitamine K2 MK-7 microencapsulée - Laboratoire UNAE
=> Après 3 mois, K2 MK7 ne possède plus que 30 % de son intégrité / efficacité, 1% après 12 mois.
=> After 3 months, K2 MK7 only has 30% of its integrity / efficiency, 1% after 12 months.
25) Menaquinone 7 Stability of Formulations and Its Relationship with Purity Profile
doi: 10.3390/molecules24050829
=> Results showed higher purity profile results in enhanced stability, and this could explain title discrepancies found in finished products.
26) Stability of vitamin K2 as vitaMK7
Stability of vitamin K2 as vitaMK7

 

[LeeLemonoil]

K1 converts to every needed form of K in vivo.
Also, newer research indicates that animal foods like meat and dairy, eggs contain lot of long-chain menaquinones/Vit K mk11-17 or some such osik.

I think the debate mk4 vs mk7 is about a non-issue. We all likely get enough K by eating vegetables and meat

 

[SOMO]

K1 converts to every needed form of K in vivo.
Also, newer research indicates that animal foods like meat and dairy, eggs contain lot of long-chain menaquinones/Vit K mk11-17 or some such osik.

I think the debate mk4 vs mk7 is about a non-issue. We all likely get enough K by eating vegetables and meat

The K1 conversion happens by gut bacteria.

What guarantee does anyone have that they have the correct bacteria to produce K2 from K1?
How do we know we have enough of the bacteria to produce adequate (high) doses of K2?

 

[Mito]

The K1 conversion happens by gut bacteria.

I don’t think there is any evidence that gut bacteria conversion contributes a significant amount of K2. The conversion happens in the intestinal cells. It seems the evidence for how good we are at the conversion is not well understood. I’d speculate it depends on metabolic health and more specifically intestinal health.

“When we consume any form of vitamin K, our intestinal cells break the side chains off of a small portion to yield the pure ring structure, known as menadione (Thijssen, 2006). Menadione then disperses through the body to many tissues that convert it to MK-4 for their own use by adding MK-4’s characteristic four-unit unsaturated side chain (Hirota, 2013).

We have known that animals synthesize MK-4 from other K vitamins for over a half century. It has been clear throughout that time, however, that the conversion varies widely. Early experiments, for example, showed that birds made the conversion better than rats and pigeons made it better than other birds (Billeter, 1960). Among rats, Wistar rats (Thijssen, 1994) seem to make the conversion better than Lewis rats (Ronden, 1998). Since the conversion varies between and within species, we should not assume that we as humans can make the conversion efficiently and consistently enough to meet our needs.

And just how good are we at this conversion? We really don’t know, but it stands to reason that it varies from person to person. Rare genetic defects in Ubiad1 have been identified (Yellore, 2007), and cancer is associated with epigenetic silencing of Ubiad1 (Woolston, 2015). Other genes involved in the conversion likely vary from person to person as well, but we don’t yet know what they are. One of them may be vitamin K epoxide oxidoreductase (VKOR), the target of warfarin. The normal role of VKOR is to reduce vitamin K that has been oxidized, and we know that menadione must be in a reduced state to undergo conversion to MK-4. Indeed, warfarin prevents the conversion of K1 to MK-4 in rats (Spronk, 2003). Genetic polymorphisms in VKOR are common (Shearer, 2012), and could hypothetically contribute to variation in MK-4 synthesis. We still do not know what enzyme is responsible for cleaving the side chain within our intestinal cells, and that could be polymorphic as well.

However good or bad humans may naturally be at the conversion, many people are taking medications that inhibit it (Hirota, 2015). Lipophilic statins such as lovastatin and simvastatin (and presumably atorvastatin, branded as Lipitor) inhibit the conversion. So do nitrogen-containing bisphosphonates such as alendronate (Fosamax) and zolendronate (Zometa), and presumably other nitrogenous bisphosphates as well. Ubiad1 expression depends on zinc (Funahashi, 2015) and its enzymatic activity depends on magnesium (Hirota, 2015), suggesting that deficiencies of either of these minerals could also compromise the conversion.

Finally, if we converted other K vitamins to MK-4 on a “however much we need to” basis, then it shouldn’t matter what type of vitamin K we consume at all. All forms of vitamin K generate some menadione in the intestine that can be converted to MK-4 in other tissues. Whether the menadione comes from K1, MK-4, MK-7, or any other form of vitamin K cannot make any difference in its tissue distribution. Humans accumulate MK-4 in multiple organs including the heart, lung, brain, liver, kidney, and pancreas (Thijssen, 1996). Thus, if there are no major limitations on the conversion besides our need for it, K1 should be perfectly capable of supplying these tissues with all the MK-4 they need, especially in populations that have high K1intakes. Yet this does not seem to be what we find.

Consider the Dutch population, where this has been investigated most extensively. K1 intakes are eight times higher than K2 intakes, yet only K2 intake is inversely correlated with heart disease (Geleijnse, 2004; Gast, 2009; Buelens, 2009; Zwakenberg, 2016). In Germany, K1 intakes are about three times higher than K2 intakes, yet only K2intake is inversely correlated with advanced prostate cancer (Nimptsch, 2008) and lung cancer (Nimptsch, 2010).

These observational studies don’t offer clear evidence of cause-and-effect relationships and they don’t show correlations with health endpoints that are specific to MK-4. However, they do add to the list of reasons to believe that our ability to synthesize MK-4 is limited by much more than our specific need for MK-4 itself, and by much more than our general need for vitamin K in the tissues that unconverted K1 has a hard time reaching. In other words, many of us probably need more MK-4 than we can make on our own, and that’s a good reason to eat foods that provide it.

Altogether, the evidence suggests that the form of vitamin K we consume matters, and that we are best served by a diversity of K vitamins from leafy greens, animal foods, and fermented foods.”
The Ultimate Vitamin K2 Resource | Chris Masterjohn, PhD

 

[SOMO]

I don’t think there is any evidence that gut bacteria conversion contributes a significant amount of K2. The conversion happens in the intestinal cells. It seems the evidence for how good we are at the conversion is not well understood. I’d speculate it depends on metabolic health and more specifically intestinal health.

“When we consume any form of vitamin K, our intestinal cells break the side chains off of a small portion to yield the pure ring structure, known as menadione (Thijssen, 2006). Menadione then disperses through the body to many tissues that convert it to MK-4 for their own use by adding MK-4’s characteristic four-unit unsaturated side chain (Hirota, 2013).

We have known that animals synthesize MK-4 from other K vitamins for over a half century. It has been clear throughout that time, however, that the conversion varies widely. Early experiments, for example, showed that birds made the conversion better than rats and pigeons made it better than other birds (Billeter, 1960). Among rats, Wistar rats (Thijssen, 1994) seem to make the conversion better than Lewis rats (Ronden, 1998). Since the conversion varies between and within species, we should not assume that we as humans can make the conversion efficiently and consistently enough to meet our needs.

And just how good are we at this conversion? We really don’t know, but it stands to reason that it varies from person to person. Rare genetic defects in Ubiad1 have been identified (Yellore, 2007), and cancer is associated with epigenetic silencing of Ubiad1 (Woolston, 2015). Other genes involved in the conversion likely vary from person to person as well, but we don’t yet know what they are. One of them may be vitamin K epoxide oxidoreductase (VKOR), the target of warfarin. The normal role of VKOR is to reduce vitamin K that has been oxidized, and we know that menadione must be in a reduced state to undergo conversion to MK-4. Indeed, warfarin prevents the conversion of K1 to MK-4 in rats (Spronk, 2003). Genetic polymorphisms in VKOR are common (Shearer, 2012), and could hypothetically contribute to variation in MK-4 synthesis. We still do not know what enzyme is responsible for cleaving the side chain within our intestinal cells, and that could be polymorphic as well.

However good or bad humans may naturally be at the conversion, many people are taking medications that inhibit it (Hirota, 2015). Lipophilic statins such as lovastatin and simvastatin (and presumably atorvastatin, branded as Lipitor) inhibit the conversion. So do nitrogen-containing bisphosphonates such as alendronate (Fosamax) and zolendronate (Zometa), and presumably other nitrogenous bisphosphates as well. Ubiad1 expression depends on zinc (Funahashi, 2015) and its enzymatic activity depends on magnesium (Hirota, 2015), suggesting that deficiencies of either of these minerals could also compromise the conversion.

Finally, if we converted other K vitamins to MK-4 on a “however much we need to” basis, then it shouldn’t matter what type of vitamin K we consume at all. All forms of vitamin K generate some menadione in the intestine that can be converted to MK-4 in other tissues. Whether the menadione comes from K1, MK-4, MK-7, or any other form of vitamin K cannot make any difference in its tissue distribution. Humans accumulate MK-4 in multiple organs including the heart, lung, brain, liver, kidney, and pancreas (Thijssen, 1996). Thus, if there are no major limitations on the conversion besides our need for it, K1 should be perfectly capable of supplying these tissues with all the MK-4 they need, especially in populations that have high K1intakes. Yet this does not seem to be what we find.

Consider the Dutch population, where this has been investigated most extensively. K1 intakes are eight times higher than K2 intakes, yet only K2 intake is inversely correlated with heart disease (Geleijnse, 2004; Gast, 2009; Buelens, 2009; Zwakenberg, 2016). In Germany, K1 intakes are about three times higher than K2 intakes, yet only K2intake is inversely correlated with advanced prostate cancer (Nimptsch, 2008) and lung cancer (Nimptsch, 2010).

These observational studies don’t offer clear evidence of cause-and-effect relationships and they don’t show correlations with health endpoints that are specific to MK-4. However, they do add to the list of reasons to believe that our ability to synthesize MK-4 is limited by much more than our specific need for MK-4 itself, and by much more than our general need for vitamin K in the tissues that unconverted K1 has a hard time reaching. In other words, many of us probably need more MK-4 than we can make on our own, and that’s a good reason to eat foods that provide it.

Altogether, the evidence suggests that the form of vitamin K we consume matters, and that we are best served by a diversity of K vitamins from leafy greens, animal foods, and fermented foods.”
The Ultimate Vitamin K2 Resource | Chris Masterjohn, PhD

It's great news if we are able to convert K1 to MK4 without gut-bacteria because antibiotics are suggested as adjunctive supplements on this forum.

The next concern would be if someone has a damaged intestine (damage to microvilli, lesions, diverticulitis, or leaky gut) does this conversion still happen and is it reduced?

If the conversion happens in the intestine with or without the aid of the microbiome, I still think supplementation might be warranted in some people. If MK4 accumulates in organs as you stated, then organ meats would be a good source. I'm one of the few that enjoy natto, but the average person will find it repulsive and when I do eat natto, I try to eat it away from family.

Maybe in 10 years we will know just how much K1 is converted and how much K2 is produced internally, until then - leafy greens, cheese, organ meats and supplements are all we can do.

 

[Apple]

“Later studies, in which the long-chain menaquinone-7 (MK-7) was used to counteract warfarin-induced calcification, showed that this form of menaquinone was even more potent than menaquinone-4. ”

The Role of Vitamin K in Soft-Tissue Calcification

 

[ddjd]

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)

could this possibly explain why i got shingles after taking k1 for too long??
interestingly i noted aspirin significantly helped me recover from the shingles

 

[LucH]

I don’t think so. Too much quinone is not advised, however. Same family as tocopherols (Vit E) and menaquinones (Vit K2).

Quinones generate reactive oxygen species through redox cycling. Oxidation of tocopherols and tocotrienols produces para- and ortho-quinones, and quinone methides, while oxidation of their carboxyethyl hydroxychroman derivatives produces quinone lactones (cytotoxicity of excess quinones).

Too many quinones could interfere with hormesis. Too much of a good thing is deleterious.

Aspirin is ok when taking too much K1 (coagulation not desired).

Info on absorption, target and dosage of vitamin K (and links from Chris Masterjohn and Kate Rheaume-blue) (in French, with English links).

 

[LOL]

I've tried two different brands of MK-7 and both gave me a slight feeling of vertigo that increased with continued use. With the first brand I took 150 mcg once daily and with the second 75 mcg once daily. I eat beef liver weekly, drink milk and take a D3 supplement (80 mcg/daily, no sun here).
With MK-4 I never noticed any side effects although I took much higher doses, sometimes up to 15 mg/daily.
So there's definitively a difference, hard to say exactly what - whether it's a general low-quality of MK-7 supplements or physiological effect.

 

[Rafael Lao Wai]

According to Chris Materjohn's article on vitamin K2, beef liver has mostly MK-7( around 100 micrograms per 100 grams), so, assuming that the liver of cows in the wild also has mostly this form of K2( which can be a wrong assumption), then it's not out of realm of possibility that our organism got used to ingesting at least some MK-7 frequently.

Also, the japanese have nice square jaws, so that makes me think that, either the MK-7 has this effect just like MK-4, or the former is helping preserve the latter, thus the jaw widening effect.

Currently, I'm experimenting with spinach( boiled to remove some of the oxalates), about 200 grams a day. That contains close to 1 mg of vitamin K1( phylloquinone). It certainly lowers my bleeding time. I also noticed joint benefits, especifically for the right hip joint. I found out that cooked fiber is much milder on my gut, and I don't get pretty much any pain from it, so that's nice.

 

[Rafael Lao Wai]

I'm not sure if the info on beef liver was changed or I just remembered it wrong( probably the latter), but I was checking the k2 content of it again, and it seems to have a mix of various lengths of MK. The biggest amounts are in the form of MK-7, 11, 12 and 13:

Search Results |

chrismasterjohnphd.com

 

[Coderr]

I consume dried parsley because of its apigenin content. There is a high amount of vitamin K in parsley. Will this help me build mk-4?

 

[MyUsernameHere]

MK7 is so weird man. It just dampens me mentally, in a sense. I've read some studies claiming it inhibits 5-AR. I definitely don't feel quite right. At 200 mcg daily I also had chest pains.

MK4 has more of a testo-boosting, anti-estrogen feeling. I like it more generally. Can tolerate up to 5 mg, above that, weird bone pains happen.

 

[Daniil]

I find this question difficult, has anyone asked Ray what he thinks about it? Can I use K2 MK7 when taking aspirin, and how much?

 

[Frankdee20]

I find this question difficult, has anyone asked Ray what he thinks about it? Can I use K2 MK7 when taking aspirin, and how much?

I’m sure