Menaquinone 4 increases plasma lipid levels in hypercholesterolemic mice

[Belsazar]

Found this mouse study on K2/MK4. Menaquinone 4 increases plasma lipid levels in hypercholesterolemic mice (https://doi.org/10.1038/s41598-021-82724-0)

Interesting, since negative studies on mk4 are rare and megadosing is advocated on this forum. They tested MK4 effects on a hypercholesterolemic mouse model and found hepatic steatosis. Should those of us with a fatty liver be concerned? Can it induce/worsen hepatic steatosis in humans (I am not aware of any studies so far)? Any input appreciated.

Here, we demonstrate that MK4 caused a deranged plasma lipid profile without affecting the aortic valve morphology in LDLr−/−ApoB100/100 mice. The mice consuming the MK4 diet had increased plasma levels of LDL and triglycerides, hepatic steatosis, and mRNA expression of hepatic genes required for triglyceride and cholesterol metabolism. Consequently, MK4 may have non-beneficial effects on lipid levels, especially in the presence of hypercholesterolemia.

 

[schultz]

Could be the type of mouse used. Apparently it lowered both inflammatory and anti-inflammatory cytokines. I'd love to see the study repeated with a different mouse model, or better yet a human study of some sort.

There were some interesting effects though, like reduced cytokines in the liver of K2 mice. It might do the same thing in the lung and would probably be protective for COVID-19 patients.

"However, as vitamin K has been shown to have anti-inflammatory effects, we performed a hepatic cytokine array. We detected a decline in the expression of several central inflammatory cytokines after MK4 treatment when compared to the control group (Fig. 5C). Interestingly, MK4 decreased the expression of both anti-inflammatory cytokines, e.g. interleukin 4 (IL-4) (−62%, p < 0.05), IL-5 (−69%, p < 0.01), IL-9 (−69%, p < 0.05), and pro-inflammatory cytokines e.g. IL-6 (−64%, p < 0.05), IL-12p40 (−66%, p < 0.05), IL-12p70 (−62%, p < 0.05) and IL-13 (−61%, p < 0.05). In addition, the protein levels of tumour necrosis factor α (TNFα) (−63%, p < 0.05) and interferon-γ (IFN-γ) (−72%, p < 0.01) were markedly reduced, as well as those of the chemokines, monocyte chemoattractant protein 1 (MCP1) (−70%, p < 0.001) and MCP5 (−65%, p < 0.05)."


And I'm very interested in this...

"In addition, a decline in Cyp3a11 and Cpt1a gene expression was detected. This is in line with the previous work of Hashimato et al., demonstrating that knockdown of CYP3a in mice led to an increase of cholesterol biosynthesis via Srebp2."


An increase in cholesterol biosynthesis would be awesome for increased hormone production. I've been trying to maximize cholesterol via fructose intake. K2 might be another tool to help with that. If I get NAFLD I'll let everyone know lol (although I take aspirin and drinks lots of coffee so I am doubting it...)


"We also found that MK4 decreased the levels of several inflammatory markers in the liver, including IL-6, MCP-1 and TNFα. This may be explained by the anti-inflammatory effects of MK4. It has been reported that MK4 can reduce the IL-6, IL1β and TNFα mRNA levels in lipopolysaccharide-induced mouse RAW264.7 and microglia-derived cells."

"Similarly, in the Framingham offspring study, excess vitamin K attenuated the general plasma inflammatory index as well as lowering the level of TNFα37. As the overall expression of both pro- and anti-inflammatory cytokines and chemokines decreased in our study, these findings may indicate that MK4 directly suppresses the hepatic nuclear factor kappa B (NF-κB) pathway which is in line with previous reports."


Anyway, thanks for sharing

 

[Belsazar]

Yes, the anti-inflammatory response looks nice, but still they found inflammation in the liver.

MK4 increases the expression of lipid metabolism regulating genes​

To study the molecular mechanisms underlying elevated plasma lipid levels, we analyzed the expression levels of inflammatory and lipid metabolism genes in liver after 18 h exposure of MK4, the expected time when changes in gene expression would be observed. We found that MK4 upregulated the mRNA expressions of triglyceride synthesis genes fatty acid synthase (Fasn,12.2-fold, p < 0.05) and sterol regulatory element binding transcription factor 1c (Srebp1c, 1.6-fold, p < 0.05), cholesterol synthesis genes 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 1 (Hmgcs1, 5.8-fold, p < 0.05), sterol regulatory element binding, factor 2 (Srebp2, 1.6-fold, p < 0.01), and also proprotein convertase subtilisin/kexin type 9 (Pcsk9, 8.6-fold, p < 0.05), a protein known to be involved in the regulation of LDL receptor degradation (Fig. 3A–E and Supplementary Table 1). Interestingly, MK4 caused reductions in mRNA expressions of the β-oxidation regulatory gene, carnitine palmitoyltransferase 1a (Cpt1a, 0.4-fold, P < 0.01) and cholesterol synthesis related gene cytochrome P450 family 3 subfamily A polypeptide 11 (Cyp3a11, 0.5-fold, p < 0.05) (Fig. 3F–G and supplementary table 1).

It seems Triglycerides and cholesterol synthesis is pushed up, but β-oxidation is reduced. Maybe the liver in these mouse model can't keep up with the export of those increased lipids in addition to not being used up by β-oxidation, which let them accumulate and cause steatosis. So the question is, how can one help the liver to reduce that effect? Why was no control performed with normal mice?

 

[schultz]

Why was no control performed with normal mice?

Yeah I was wondering that. Just money probably. It would have been interesting if they had a control group of "regular" mice and regular mice with K2.

It seems Triglycerides and cholesterol synthesis is pushed up, but β-oxidation is reduced. Maybe the liver in these mouse model can't keep up with the export of those increased lipids in addition to not being used up by β-oxidation, which let them accumulate and cause steatosis.

I really have no idea TBH, as I am not that familiar with the effects of K2 or K, but in some instances I suspect increased triglycerides and cholesterol are a defensive mechanism. This study (below) suggests something to that effect, where rats were fed fructose and saturated fat (FS group), had increased TG's but also a decrease in lipid peroxidation and increased antioxidant status.

It's possible in the study you posted that if the study were continued for a longer period of time the damage in the non K2 group could have increased and surpassed the K2 group (complete speculation). This is why it's hard to draw conclusions from a single study. But they do help direct further avenues of research, and they should at least be considered and filed away as a potential affect, especially if new information surfaces in the future.

Changes in lipid metabolism and antioxidant defense status in spontaneously hypertensive rats and Wistar rats fed a diet enriched with fructose and saturated fatty acids - PubMed

These findings clearly indicate that the FS diet did not alter blood pressure of spontaneously hypertensive rats and Wistar rats. The FS diet resulted in hypertriglyceridemia but increased the total antioxidant status, which may prevent lipid peroxidation in these rats.

pubmed.ncbi.nlm.nih.gov

"The FS diet significantly enhanced plasma and VLDL-LDL triacylglycerol concentrations without affecting concentrations of VLDL-LDL thiobarbituric acid-reactive substances. The decreased content of arachidonic acid and total polyunsaturated fatty acids in VLDL-LDL by the FS diet may have prevented lipid peroxidation in this fraction. Moreover, FS consumption by both strains was accompanied by a significant increase in total antioxidant capacity of adipose tissue, muscle, heart, and liver.

"The FS diet resulted in hypertriglyceridemia but increased the total antioxidant status, which may prevent lipid peroxidation in these rats."


And this study suggests TG's may protect against endotoxin. So it's possible if you change some variables (less endotoxin leaking through intestine via change in diet, or lower PUFA diet... PUFA also increases intestinal permeability and affects the liver) the results would look different.

Diet-induced protection against lipopolysaccharide includes increased hepatic NO production - PubMed

The host response to Gram-negative infection includes the elaboration of numerous proinflammatory agents, including tumor necrosis factor alpha (TNFalpha) and nitric oxide (NO). A component of the hepatic response to infection is an elevation in serum lipids, the so-called "lipemia of sepsis,"...

pubmed.ncbi.nlm.nih.gov

"A component of the hepatic response to infection is an elevation in serum lipids, the so-called "lipemia of sepsis," which results from the increased production of triglyceride (TG)-rich lipoproteins by the liver. We have postulated that these lipoproteins are components of a nonadaptive, innate immune response to endotoxin [lipopolysaccharide (LPS)] and have previously demonstrated the capacity of TG-rich lipoproteins to protect against endotoxicity in rodent models of sepsis."


Endotoxin is definitely connected to fatty liver in the literature.

 

[CLASH]

Yeah I was wondering that. Just money probably. It would have been interesting if they had a control group of "regular" mice and regular mice with K2.



I really have no idea TBH, as I am not that familiar with the effects of K2 or K, but in some instances I suspect increased triglycerides and cholesterol are a defensive mechanism. This study (below) suggests something to that effect, where rats were fed fructose and saturated fat (FS group), had increased TG's but also a decrease in lipid peroxidation and increased antioxidant status.

It's possible in the study you posted that if the study were continued for a longer period of time the damage in the non K2 group could have increased and surpassed the K2 group (complete speculation). This is why it's hard to draw conclusions from a single study. But they do help direct further avenues of research, and they should at least be considered and filed away as a potential affect, especially if new information surfaces in the future.

Changes in lipid metabolism and antioxidant defense status in spontaneously hypertensive rats and Wistar rats fed a diet enriched with fructose and saturated fatty acids - PubMed

These findings clearly indicate that the FS diet did not alter blood pressure of spontaneously hypertensive rats and Wistar rats. The FS diet resulted in hypertriglyceridemia but increased the total antioxidant status, which may prevent lipid peroxidation in these rats.

pubmed.ncbi.nlm.nih.gov

"The FS diet significantly enhanced plasma and VLDL-LDL triacylglycerol concentrations without affecting concentrations of VLDL-LDL thiobarbituric acid-reactive substances. The decreased content of arachidonic acid and total polyunsaturated fatty acids in VLDL-LDL by the FS diet may have prevented lipid peroxidation in this fraction. Moreover, FS consumption by both strains was accompanied by a significant increase in total antioxidant capacity of adipose tissue, muscle, heart, and liver.

"The FS diet resulted in hypertriglyceridemia but increased the total antioxidant status, which may prevent lipid peroxidation in these rats."


And this study suggests TG's may protect against endotoxin. So it's possible if you change some variables (less endotoxin leaking through intestine via change in diet, or lower PUFA diet... PUFA also increases intestinal permeability and affects the liver) the results would look different.

Diet-induced protection against lipopolysaccharide includes increased hepatic NO production - PubMed

The host response to Gram-negative infection includes the elaboration of numerous proinflammatory agents, including tumor necrosis factor alpha (TNFalpha) and nitric oxide (NO). A component of the hepatic response to infection is an elevation in serum lipids, the so-called "lipemia of sepsis,"...

pubmed.ncbi.nlm.nih.gov

"A component of the hepatic response to infection is an elevation in serum lipids, the so-called "lipemia of sepsis," which results from the increased production of triglyceride (TG)-rich lipoproteins by the liver. We have postulated that these lipoproteins are components of a nonadaptive, innate immune response to endotoxin [lipopolysaccharide (LPS)] and have previously demonstrated the capacity of TG-rich lipoproteins to protect against endotoxicity in rodent models of sepsis."


Endotoxin is definitely connected to fatty liver in the literature.

TNF-alpha is produced in response to endotoxin. TNF-alpha upregulates fatty acid synthesis and cholesterol synthesis by the liver. The cholesterol and triglycerides are exported to the blood where they directly bind to endotoxin. When they bind to endotoxin they essentially inactivate it and carry it back to the liver to be detoxified. By binding and detoxifying the endotoxin they prevent macrophages from getting hold of the endotoxin and stimulating a further inflammatory response. So the whole system is a feedback loop. The more endotoxin the more fats pushed into the blood, the more fats that bind endotoxin the less inflammatory response. This is why, while high fat meals increase serum endotoxin, they dont increase inflammation. The endotoxin is already bound to the fat so it is easily detoxified by the liver. Also, while cholesterol and triglycerides bind endotoxin, alkaline phosphatase and bile acids in the intestine directly degrade it and chylomicrons also bind it. Fat in the diet stimulates all of these components. Combine that fat with some fruit/ fruit juice and other plant compounds and you have a strong anti-endotoxin stack.

The reason why the body does all of this is because as far as I can see endotoxin is a direct mitochondrial poison.

Pure fructose feeding usually leads to large amounts of endotoxin production and endotoxin influx from the gut to the liver.

 

[lampofred]

I didn't read the study but in general I think Peat likes things which raise cholesterol production (fructose, vit D). Increased cholesterol because of increased production is a sign of being well-fed, it's only increased cholesterol because it's not being converted into hormones like preg/prog which is a sign of a problem (like low thyroid)

 

[Korven]

TNF-alpha is produced in response to endotoxin. TNF-alpha upregulates fatty acid synthesis and cholesterol synthesis by the liver. The cholesterol and triglycerides are exported to the blood where they directly bind to endotoxin. When they bind to endotoxin they essentially inactivate it and carry it back to the liver to be detoxified. By binding and detoxifying the endotoxin they prevent macrophages from getting hold of the endotoxin and stimulating a further inflammatory response. So the whole system is a feedback loop. The more endotoxin the more fats pushed into the blood, the more fats that bind endotoxin the less inflammatory response. This is why, while high fat meals increase serum endotoxin, they dont increase inflammation. The endotoxin is already bound to the fat so it is easily detoxified by the liver. Also, while cholesterol and triglycerides bind endotoxin, alkaline phosphatase and bile acids in the intestine directly degrade it and chylomicrons also bind it. Fat in the diet stimulates all of these components. Combine that fat with some fruit/ fruit juice and other plant compounds and you have a strong anti-endotoxin stack.

The reason why the body does all of this is because as far as I can see endotoxin is a direct mitochondrial poison.

Pure fructose feeding usually leads to large amounts of endotoxin production and endotoxin influx from the gut to the liver.

Do you think hypocholesterolemia can be caused by chronic endotoxin exposure from SIBO/leaky gut, where the liver after a while can't cope any longer with the endotoxin burden? Basically causing "liver exhaustion" and low cholesterol.

When I was eating a plant-based diet my cholesterol was down to 70 mg/dL. I felt like dying. By reducing starch consumption and increasing saturated fat (among other things) I've gotten it up to 160 mg/dL and feel 1000x better.

 

[lampofred]

Do you think hypocholesterolemia can be caused by chronic endotoxin exposure from SIBO/leaky gut, where the liver after a while can't cope any longer with the endotoxin burden? Basically causing "liver exhaustion" and low cholesterol.

When I was eating a plant-based diet my cholesterol was down to 70 mg/dL. I felt like dying. By reducing starch consumption and increasing saturated fat (among other things) I've gotten it up to 160 mg/dL and feel 1000x better.

What other things helped you raise cholesterol?

 

[Korven]

What other things helped you raise cholesterol?

Honestly I can't say for sure what had the most impact seeing as I've changed so many things. Most helpful was probably avoiding irritating, fibrous foods that cause gut inflammation and feed SIBO. Other than that that I've cycled through lots and lots of different anti-microbials and antibiotics that I believe helped get rid of gut infection and SIBO, allowing cholesterol to come up. Also whole milk seems to be pro-cholesterol.

 

[Belsazar]

TNF-alpha is produced in response to endotoxin. TNF-alpha upregulates fatty acid synthesis and cholesterol synthesis by the liver. The cholesterol and triglycerides are exported to the blood where they directly bind to endotoxin. When they bind to endotoxin they essentially inactivate it and carry it back to the liver to be detoxified. By binding and detoxifying the endotoxin they prevent macrophages from getting hold of the endotoxin and stimulating a further inflammatory response. So the whole system is a feedback loop. The more endotoxin the more fats pushed into the blood, the more fats that bind endotoxin the less inflammatory response. This is why, while high fat meals increase serum endotoxin, they dont increase inflammation. The endotoxin is already bound to the fat so it is easily detoxified by the liver. Also, while cholesterol and triglycerides bind endotoxin, alkaline phosphatase and bile acids in the intestine directly degrade it and chylomicrons also bind it. Fat in the diet stimulates all of these components. Combine that fat with some fruit/ fruit juice and other plant compounds and you have a strong anti-endotoxin stack.

The reason why the body does all of this is because as far as I can see endotoxin is a direct mitochondrial poison.

Pure fructose feeding usually leads to large amounts of endotoxin production and endotoxin influx from the gut to the liver.

Sounds reasonable. But where is the connection with K2MK4? Does it increase susceptibility to endotoxin?

This is the diet btw: https://insights.envigo.com/hubfs/resources/data-sheets/88137.pdf
It has more sugar than starch.

+Cholesterol (0.2% total cholesterol)
+Total fat (21% by weight; 42% kcal from fat)
+High in saturated fatty acids (>60% of total fatty acids)
+High sucrose (34% by weight)

 

[CLASH]

I didn't read the study but in general I think Peat likes things which raise cholesterol production (fructose, vit D). Increased cholesterol because of increased production is a sign of being well-fed, it's only increased cholesterol because it's not being converted into hormones like preg/prog which is a sign of a problem (like low thyroid)

Increased cholesterol isn't neccesarily a good thing. It depends on why its being increased. Cholesterol is often increased, such as the case of hyperlipidemia in the response to infection whether acute, chronic or gut derived. Its called an acute phase response. On the flip side tho, lowering cholesterol directly, as is done with modern medicine makes little sense and the benefit it marginal with some possible serious side effects. The question is why is cholesterol being raised and how? Cholesterol itself isn't neccesarilly the problem tho

Do you think hypocholesterolemia can be caused by chronic endotoxin exposure from SIBO/leaky gut, where the liver after a while can't cope any longer with the endotoxin burden? Basically causing "liver exhaustion" and low cholesterol.

When I was eating a plant-based diet my cholesterol was down to 70 mg/dL. I felt like dying. By reducing starch consumption and increasing saturated fat (among other things) I've gotten it up to 160 mg/dL and feel 1000x better.

The fibers in the plant based diet, some of the plant compounds, and the type of fats in those diets bind cholesterol and bile and pull it out of the body shunting cholesterol to bile production, force cholesterol excretion into bile directly, and impair cholesterol production at the liver, respectively. Plant base diets also often lack the necessary precursors for cholesterol production. As you mentioned they can also induce SIBO which may alter cholesterol metabolism however I dont personally know the specifics behind those mechanisms as well as I do the others. Overall, the stereotypical idea of plant based diets in modern culture are a terrible idea in my experience and my opinion theoretically.

Sounds reasonable. But where is the connection with K2MK4? Does it increase susceptibility to endotoxin?

This is the diet btw: https://insights.envigo.com/hubfs/resources/data-sheets/88137.pdf
It has more sugar than starch.

Considering that it increased the production of triglycerides and cholesterol which I alluded to as protective above and it lowered inflammatory cytokines I would say it trends to a larger picture of being protective. Not to mention that in the MK4 group, with everything going on, there was a neutral effect on aortic calcification. Also considering that this study is performed in mice, who's livers are notorious poor handlers of fats and sugars compared to humans, and that the diet was a purified lab diet its difficult to draw exact conclusions. I think a reasonable dosage of 1mg per day of MK-4 in conjunction with calcium, magnesium and vit D3 on top of solid diet (not lab based garbage like these rats are fed) should be pretty safe. However this is just my personal opinion in light of the beneficial research I've seen on MK4.

Overall I think the conclusion of this study is dont feed genetic knockout mice high amounts of anhydrous milk fat, sucrose, cornstarch, casein, cellulose, and synthetic vitamin mixtures, and think that vit K2 MK4 is going to rescue them from the resultant metabolic pathology.

 

[Belsazar]

Considering that it increased the production of triglycerides and cholesterol which I alluded to as protective above and it lowered inflammatory cytokines I would say it trends to a larger picture of being protective. Not to mention that in the MK4 group, with everything going on, there was a neutral effect on aortic calcification. Also considering that this study is performed in mice, who's livers are notorious poor handlers of fats and sugars compared to humans, and that the diet was a purified lab diet its difficult to draw exact conclusions. I think a reasonable dosage of 1mg per day of MK-4 in conjunction with calcium, magnesium and vit D3 on top of solid diet (not lab based garbage like these rats are fed) should be pretty safe. However this is just my personal opinion in light of the beneficial research I've seen on MK4.

Overall I think the conclusion of this study is dont feed genetic knockout mice high amounts of anhydrous milk fat, sucrose, cornstarch, casein, cellulose, and synthetic vitamin mixtures, and think that vit K2 MK4 is going to rescue them from the resultant metabolic pathology.

Something is going on in the MK4 treated hypercholesterolemic mouse model which was significantly different from the control which led to hepatic steatosis. Endotoxin load was the same based on the standardized diet. There is not really a different way than to have a purified diet in terms of experimental setup to really distinguish the effects of a single substance. The picture you draw might not be wrong, but still not answering the open questions in a satisfying way.

Adding Vitamin E on top of MK4 would be interesting to see, since it was shown to help against NAFLD.

 

[CLASH]

Something is going on in the MK4 treated hypercholesterolemic mouse model which was significantly different from the control which led to hepatic steatosis. Endotoxin load was the same based on the standardized diet. There is not really a different way than to have a purified diet in terms of experimental setup to really distinguish the effects of a single substance. The picture you draw might not be wrong, but still not answering the open questions in a satisfying way.

Adding Vitamin E on top of MK4 would be interesting to see, since it was shown to help against NAFLD.

Thats because there isn't a satisfying answer to be drawn from one study of this sort. Multiple studies have to be looked at to get an idea, in my experience.

Both the control group and the MK4 group had hepatic steatosis. The MK4 group just had more. This makes sense considering the MK4 group upregulated the triglyceride synthesis and cholesterol synthesis compared to control. The issue may be with the ability of the liver to desaturate the de novo synthesized lipids and export them to the plasma and tissues. However, its important to recognize the MK4 group lowered inflammatory cytokines, and inflammatory response in general. If it somehow deranged the metabolic pathway of the coordinated response than perhaps thats why it lead to the increased steatosis; perhaps to the mechanisms I alluded to above. The question still remains, "why did it do this" and its a valid question. Its something to look into further, but at the moment not for me.

Also, the endotoxin and cholesterol points I discussed above were not in direct response to your post, they were in response to others posts. I wasn't trying to make points to the study in that regard.

 

[Belsazar]

Thats because there isn't a satisfying answer to be drawn from one study of this sort. Multiple studies have to be looked at to get an idea, in my experience.

Both the control group and the MK4 group had hepatic steatosis. The MK4 group just had more. This makes sense considering the MK4 group upregulated the triglyceride synthesis and cholesterol synthesis compared to control. The issue may be with the ability of the liver to desaturate the de novo synthesized lipids and export them to the plasma and tissues. However, its important to recognize the MK4 group lowered inflammatory cytokines, and inflammatory response in general. If it somehow deranged the metabolic pathway of the coordinated response than perhaps thats why it lead to the increased steatosis; perhaps to the mechanisms I alluded to above. The question still remains, "why did it do this" and its a valid question. Its something to look into further, but at the moment not for me.

Also, the endotoxin and cholesterol points I discussed above were not in direct response to your post, they were in response to others posts. I wasn't trying to make points to the study in that regard.

Sure, I will keep reading around those topics and it's what I was speculating as well. For me it leads to the obvious question if in context of high cholesterol/triglycerides (which the mouse model tries to resemble), mk4 supplementation (especially high dose) should be avoided. This would be a quite novel piece of information in the world of Vitamin K. Or in case of NASH/NAFLD or in case of a high fat diet, (which would be a bit paradox since mk4 needs a high fat intake for its absorption). Or Im not having all the necessary information yet and MK4 indeed leans out the liver somehow and actually improves liver health as stated often in this forum. Thats why the thread was started, to discuss it.


Menaquinone 4 Alters Plasma Lipid Profile In Hypercholesterolemic Mice
Is this the previous study? Its a bit weird, because there is no full text...

 

[Peatness]

As someone who has been using high dose vitamin K2 mk4 for many years I am curious about this study

Menaquinone 4 increases plasma lipid levels in hypercholesterolemic mice - Scientific Reports

In calcific aortic valve disease (CAVD) progressive valvular calcification causes aortic valve dysfunction. CAVD has several risk factors such as age and dyslipidemia. Vitamin K was shown to inhibit vascular calcification in mice and valvular calcification in patients with CAVD. We studied the...

www.nature.com

Anyone one else experienced high cholesterol from using this form of vitamin k2?

 

[Belsazar]

As someone who has been using high dose vitamin K2 mk4 for many years I am curious about this study

Menaquinone 4 increases plasma lipid levels in hypercholesterolemic mice - Scientific Reports

In calcific aortic valve disease (CAVD) progressive valvular calcification causes aortic valve dysfunction. CAVD has several risk factors such as age and dyslipidemia. Vitamin K was shown to inhibit vascular calcification in mice and valvular calcification in patients with CAVD. We studied the...

www.nature.com

Anyone one else experienced high cholesterol from using this form of vitamin k2?

Did you experience it or are you just refering to the study?