Vitamin K can regenerate the liver

[Mauritio]

I've been trying to find evidence for the mechanism of action of all vitamin K forms on regenerating/helping the liver.
The MoAs mentioned on this forum are kind of vague in my opinion. I do think vitamin K can be very helpful for the liver in many ways and I think the specific MoA deserves more attention.

I know georgi mentioned something about the kupfer cells. And ray said it helps support the function of CoQ10. So that's 2 mechanisms already.

This study mentions that vitamin K2 increases the hepatic progenitor cells (oval cells in rodents) and Matrillin-2 and by this mechanism helps the liver to regenerate after partial hepatectomy.


Matrillin-2 is a protein, which "promotes neurite outgrowth, Schwann cell migration, neuromuscular junction formation, skeletal muscle and liver regeneration and skin wound healing."
(Matrilin-2, an extracellular adaptor protein, is needed for the regeneration of muscle, nerve and other tissues - PubMed)

The effect was dose-dependant, so more K2 = more liver regeneration.
They also showed that blocking the increase of Matrillin-2 largely stopped the liver regeneration, showing that the regeneration was depending on this protein.

Unfortunately I couldn't find the full text, so I dont know which form of vitamin K2 and what dosage they used.

Vitamin K2-enhanced liver regeneration is associated with oval cell expansion and up-regulation of matrilin-2 expression in 2-AAF/PH rat model - PubMed

Normal liver has a great potential of regenerative capacity after partial hepatectomy. In clinic, however, most patients receiving partial hepatectomy are usually suffering from chronic liver diseases with severely damaged hepatocyte population. Under these conditions, activation of hepatic...

pubmed.ncbi.nlm.nih.gov

 

[Perry Staltic]

Full paper

https://www.researchgate.net/profile/Pijiang-Sun/publication/258631988_Vitamin_K2-Enhanced_Liver_Regeneration_is_Associated_with_Oval_Cell_Expansion_and_Up-Regulation_of_Matrilin-2_Expression_in_2-_AAFPH_Rat_Model/links/0deec53b2af384b1e6000000/Vitamin-K2-Enhanced-Liver-Regeneration-is-Associated-with-Oval-Cell-Expansion-and-Up-Regulation-of-Matrilin-2-Expression-in-2-AAF-PH-Rat-Model.pdf

 

[ecstatichamster]

K2 MK4 and coffee are extremely helpful for the liver. The liver is well known to be an organ that is particularly prone to regenerate and regrow and recover from even serious liver disease. I think fatty liver is caused by PUFAs, although there are a lot of dubious studies that say otherwise.

 

[Mauritio]

Full paper

https://www.researchgate.net/profile/Pijiang-Sun/publication/258631988_Vitamin_K2-Enhanced_Liver_Regeneration_is_Associated_with_Oval_Cell_Expansion_and_Up-Regulation_of_Matrilin-2_Expression_in_2-_AAFPH_Rat_Model/links/0deec53b2af384b1e6000000/Vitamin-K2-Enhanced-Liver-Regeneration-is-Associated-with-Oval-Cell-Expansion-and-Up-Regulation-of-Matrilin-2-Expression-in-2-AAF-PH-Rat-Model.pdf

Thanks. How did you get it, if I may ask? It wasn't on scihub

 

[Perry Staltic]

Thanks. How did you get it, if I may ask? It wasn't on scihub.

Checked Scihub first (no luck), then used a search engine and checked the various links. It was near the top of the list.

 

[Mauritio]

... so the dosage was quite high. An HED of 125/250mg. Based on that fact I'd guess it was K2MK4 that they used.

They hypothesize that the underlying MoA was activation of the steroid and xenobiotic receptor (SXR).

"Therefore, it is plausible that vitamin K2 treatment activates SXR in liver oval cells, resulting in matrilin-2 up-regulation and oval cell proliferation."

 

[Mauritio]

... so the dosage was quite high. An HED of 125/250mg. Based on that fact I'd guess it was K2MK4 that they used.

They hypothesize that the underlying MoA was activation of the steroid and xenobiotic receptor (SXR).

"Therefore, it is plausible that vitamin K2 treatment activates SXR in liver oval cells, resulting in matrilin-2 up-regulation and oval cell proliferation."

Activation of the PXR/SXR is an interesting thing in and of itself. It increases phase 1,2 and 3 detoxification in the liver and increases CYP3A4. Other ligands are for example: progesterone, 5aDHP or bile acids.

Pregnane X receptor - Wikipedia

en.m.wikipedia.org

 

[Mauritio]

PXR/SXR also upregulates a protein that takes up and excretes prostaglandins. So vitamin K leads to less PUFA/prostaglandin metabolites and damage.

Solute carrier organic anion transporter family member 2A1 - Wikipedia

en.m.wikipedia.org

Vitamin K actually has remarkable anti-PUFA and anti-oxidant capabilities.

Here are some studies on it:

(Kinetic study of free-radical-scavenging action of biological hydroquinones (reduced forms of ubiquinone, vitamin K and tocopherol quinone) in solution - PubMed)

(The potent antioxidant activity of the vitamin K cycle in microsomal lipid peroxidation - PubMed)

(Kinetic study of free-radical-scavenging action of biological hydroquinones (reduced forms of ubiquinone, vitamin K and tocopherol quinone) in solution - PubMed)

(Vitamin K prevents oxidative cell death by inhibiting activation of 12-lipoxygenase in developing oligodendrocytes - PubMed)

 

[haidut]

I've been trying to find evidence for the mechanism of action of all vitamin K forms on regenerating/helping the liver.
The MoAs mentioned on this forum are kind of vague in my opinion. I do think vitamin K can be very helpful for the liver in many ways and I think the specific MoA deserves more attention.

I know georgi mentioned something about the kupfer cells. And ray said it helps support the function of CoQ10. So that's 2 mechanisms already.

This study mentions that vitamin K2 increases the hepatic progenitor cells (oval cells in rodents) and Matrillin-2 and by this mechanism helps the liver to regenerate after partial hepatectomy.


Matrillin-2 is a protein, which "promotes neurite outgrowth, Schwann cell migration, neuromuscular junction formation, skeletal muscle and liver regeneration and skin wound healing."
(Matrilin-2, an extracellular adaptor protein, is needed for the regeneration of muscle, nerve and other tissues - PubMed)

The effect was dose-dependant, so more K2 = more liver regeneration.
They also showed that blocking the increase of Matrillin-2 largely stopped the liver regeneration, showing that the regeneration was depending on this protein.

Unfortunately I couldn't find the full text, so I dont know which form of vitamin K2 and what dosage they used.

Vitamin K2-enhanced liver regeneration is associated with oval cell expansion and up-regulation of matrilin-2 expression in 2-AAF/PH rat model - PubMed

Normal liver has a great potential of regenerative capacity after partial hepatectomy. In clinic, however, most patients receiving partial hepatectomy are usually suffering from chronic liver diseases with severely damaged hepatocyte population. Under these conditions, activation of hepatic...

pubmed.ncbi.nlm.nih.gov

I don't think I have ever said vitamin K can "regenerate" the liver. The liver is one of the few organs that can fully regenerate itself if it is provided with the needed nutrients and supportive (non-inflammatory environment). Vitamin K can certainly help with liver damage (especially fibrosis), inflammation, cancer, etc. Search PubMed (or just Google) for "menatetrenone liver cancer" or "menatetrenone hepatocellular carcinoma" (no quotes when you search) and you will find a lot of information on the topic.
The study you found is also a good one but I think its findings apply also to vitamin D, aspirin, etc since AFAIK they all affect the matrillin proteins as well.

 

[Mauritio]

I don't think I have ever said vitamin K can "regenerate" the liver. The liver is one of the few organs that can fully regenerate itself if it is provided with the needed nutrients and supportive (non-inflammatory environment). Vitamin K can certainly help with liver damage (especially fibrosis), inflammation, cancer, etc. Search PubMed (or just Google) for "menatetrenone liver cancer" or "menatetrenone hepatocellular carcinoma" (no quotes when you search) and you will find a lot of information on the topic.
The study you found is also a good one but I think its findings apply also to vitamin D, aspirin, etc since AFAIK they all affect the matrillin proteins as well.

I meant it more in broader sense , as in helping the liver . IIRC your comment specifically was on fatty liver. I saw those studies on liver cancer. Fibrosis or NAFLD I can't recall.

Then vitamin D and aspirin probably also activate PXR or have a PXR-independant mechanism of affecting matrilin-2 .
The PXR activation was responsible for the increase in matrilin-2, so other PXR-agonists as progesterone, allopregnanolone, 5aDHP or bile acids like TUDCA should also work.

 

[David PS]

How did you get it, if I may ask? It wasn't on scihub

I use Google scholar as a last resort. Here is a search using part of the title of the paper. I can quickly see the sites that have a pdf or the full text.

Google Scholar

scholar.google.com

 

[Mauritio]

I use Google scholar as a last resort. Here is a search using part of the title of the paper. I can quickly see the sites that have a pdf or the full text.

Google Scholar

scholar.google.com

Saved it . Thanks.

 

[laleto12]

is there any merit to mk7?

 

[Mauritio]

is there any merit to mk7?

Theoretically not. Although chris masterjohn says it stays in the liver more and longer.

I'm trying it right now. I'm taking just 100mcg , with MK4 I'm taking 30-50 times the amount and I feel less. Its only been 3 days though, so I'll wait a few weeks before I can give a more conclusive review. But so far it feels way more potent than MK4.

 

[laleto12]

Theoretically not. Although chris masterjohn says it stays in the liver more and longer.

I'm trying it right now. I'm taking just 100mcg , with MK4 I'm taking 30-50 times the amount and I feel less. Its only been 3 days though, so I'll wait a few weeks before I can give a more conclusive review. But so far it feels way more potent than MK4.

do you take it orally or topically?
i ve read mk7 is 5ar inhibitor which is annoying.

 

[Mauritio]

do you take it orally or topically?

Orally with food.

 

[Mauritio]

In this study women with viral liver cirrhosis had a 450% lower chance of getting liver cancer if they got Vitamin K2MK4 (45mg/d).
The number of participants was realtively low, but the results are imoressive anyway.
- Role of vitamin K2 in the development of hepatocellular carcinoma in women with viral cirrhosis of the liver - PubMed
Here they talk about the mechanism:
- Vitamin K2 Inhibits Hepatocellular Carcinoma Cell Proliferation by Binding to 17β-Hydroxysteroid Dehydrogenase 4 - PubMed

 

[Highserotonin90]

K2 MK7 drove me to delirium, but maybe it's just my predisposition due to the high brain inflammation. I had only taken 50 mcg...I would like to know more about its interactions.

 

[Ismail]

In this study women with viral liver cirrhosis had a 450% lower chance of getting liver cancer if they got Vitamin K2MK4 (45mg/d).
The number of participants was realtively low, but the results are imoressive anyway.
- Role of vitamin K2 in the development of hepatocellular carcinoma in women with viral cirrhosis of the liver - PubMed
Here they talk about the mechanism:
- Vitamin K2 Inhibits Hepatocellular Carcinoma Cell Proliferation by Binding to 17β-Hydroxysteroid Dehydrogenase 4 - PubMed

Wow amazing find!

Excuse my ignorance, what’s the “d” in 45mg/d stand for? Decilitre?! Idk

K2 MK7 drove me to delirium, but maybe it's just my predisposition due to the high brain inflammation. I had only taken 50 mcg...I would like to know more about its interactions.

How did you make that correlation? ie due to high brain inflammation? (Genuinely asking)

 

[dukesbobby777]

Wow amazing find!

Excuse my ignorance, what’s the “d” in 45mg/d stand for? Decilitre?! Idk

Per day