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I use my You Tube Live! channel to get people to recognize that they have insulin resistance or other conditions that lead to heart attack and stroke. Most people that have these problems don’t know it. They just begin growing plaque for 20 years and, suddenly, they have a heart attack or a stroke, and they’re surprised.

One interesting topic about plaque is Vitamin K2. What’s all this buzz about K2? Sometimes, it feels like there’s a lot more heat than light around this.

Here’s my history on K2.  I’d never heard of it until a couple of years ago. I heard about it from a viewer. I didn’t know it was related to calcium. 

 

 

So, I started doing some research because calcium deposition plays an important role on plaque growth. It turns out Vitamin k2 does appear to have an impact on calcium deposition and removal from bones, as well as diabetes.  

I got motivated to read the book “Vitamin K2 and the Calcium Paradox”. Written by a Doctor of Nutrition Kate Rheaume-Bleue. I saw and read about the topic and watched some of her videos.  I felt she was overstating,  or at least implying some things in the science that weren’t quite there. I’m not saying she’s misrepresented. I’m saying she does get a little bit too aggressive in terms that everything’s since we’re no longer eating cows or other animals that eat grass.

 

Vitamin K2 and the Calcium Paradox

 

Nonetheless, the science and scientific evidence present in the book really hooked me. It has to do with a thing called osteocalcin. I was totally unaware of that entire metabolic process until I started reading this book and investigating vitamin k2, phylloquinone, MK-4, and MK-7. 

There is also important evidence of the impact of osteocalcin in calcium deposition, removal from bones and in diabetes.

 

 

The Matrix gla Protein

There is a review about an article from the American College of Cardiology (ACC). This article was published on June 16, 2015, under the title “Vascular Calcification, Arterial Damage, and decline in Renal Function May be Triggered by the Inhibition of the Vitamin K-Dependent Protein Matrix Gamma-Carboxyglutamic acid (gla/MGP) by vitamin k antagonists.”

Basically, the story is this. We have known for a long time that people on K1 inhibitors (specifically warfarin) tend to get a significant increase in calcification of their arteries. 

The connection with K2 involves the GLA- the matrix protein, which according to the article, has a significant impact on calcium deposition. It is also impacted by an enzyme, the matrix gla-protein that actually is dependent on vitamin k, so medications like warfarin, when they block vitamin k1, they block k1’s ability to change this gla-protein. 

This is the matrix gla-protein. It’s non-carboxylated, so it’s not active.

 

Vascular Calcification

 

There’s a process called “gamma- carboxylation” that activates this matrix gla-protein. However, vitamin K antagonists (like warfarin) stop that gamma-carboxylation; If warfarin stops that gamma-carboxylation, then the matrix gla-protein cannot be activated. If it’s not activated, it can’t participate in helping pull calcium out of the arteries. That’s the connection and it has to do with inhibition of an activator. 

You are maybe thinking about, “Well, wait a minute. This is all K1, Brewer. We’re talking about K2. They’re very different.”  I understand that but as I said earlier, there is a connection in this metabolism, and it has to do with the carboxylation.

If you look at warfarin metabolism, it blocks vitamin K reductase and oxidation of vitamin K.  Therefore, it blocks the development of MGP.

 

warfarine_metabolism

 

Here’s another way of looking at it. It starts to get back to the vitamin K2, also known as menaquinone. The matrix gla-protein… remember that? If you want to activate the matrix gla-protein, you need to carboxylate it. The matrix gla-protein decreases calcium and therefore inhibits vascular calcification.

 

 

Vitamin K2 (part 3): Prediabetes & Inflammation – Multiple Roles

Vitamin K2 there appears to have multiple roles in the body:  A role with calcium, a role with insulin resistance, a role with inflammation

But let’s take things slow and easy so I will start by explaining a bigger issue of biology. It is what we call pleiotropic roles. 

What do we mean whit pleiotropic roles? The short version is it´s multiple roles from the same thing, but we want to go deeper than that. Pleiotropic, if you look it up on Google, says “producing or having multiple effects”. 

 

 

In medicine we see this often in a field called genetics. We have pleiotropic genes, for example, the Marfan’s gene.  It creates long finger, thin body, misshapen chest, mitral valve problems, joint problems, eye problems, a lot of things that may seem to be unrelated.

 

 

Another example of this phenomenon is when you take simple medications, such as the good old-fashioned Benadryl, an antihistamine.  It’s given for nausea, sleep, and as anti-allergy medicine. That’s the most common use. It’s also taken for itch in anti-itching. So again, multiple uses for that antihistamine. Until you begin to understand things a little bit better, they may seem unrelated.

With drugs, we often call these pleiotropic effects as “side effects.”

 

 

These different effects may seem unrelated until you go a little bit deeper. For example, with Benadryl, what does sleep have to do with anti-allergy? What does that have to do with itching? 

All of that basically has to do with histamine. And this is an antihistamine. When it blocks histamine, it starts having all these different effects – pleomorphic effects. 

Just like Marfan´s gene that changes the way the body makes connective tissue. Places where connective tissue is a big deal in terms of the shape of the chest, how long are the fingers, our eyes, and the aorta. It can kill Marfan patients at age 30-mitral valve. These are the Marfan’s gene impact on connective tissue.

Pleiotropic- meaning multiple uses or multiple roles

You may remember we’ve talked about pleiotropic effects before, specifically with statins, just to let you know, most of the times I recommend use of statins, it must do more with the pleiotropic mechanism, or “side effect” which is its impact on cardiovascular inflammation.

Pleiotropic effect of Statins on inflammation

 

 

The pleiotropic roles of statins are related with insulin, and as you probably are already thinking, yes! Insulin has significant pleiotropic effects too. 

For example, if you inject insulin into the nose, it will go past the blood-brain barrier. Once insulin goes past the blood-brain barrier and gets into the brain, it has a whole different set of mechanisms.  Most of them revolve around the hippocampus, and the biological biochemical mechanisms of memory formation. 

 

Pleiotropic (CNS effects of Insulin; e. g. memory)

 

 

Back to heart attack/stroke and K2

First, and to set things clear, one of the main functions of k2 is carboxylate enzymes.

Up to date, we know a couple of enzymes that are important in several processes that need to be carboxylated by k2 such as MGP (matrix gla protein).

The other enzyme that k2 carboxylates is osteocalcin, you can see it in several places here. These enzymes have a lot to do with calcification of the bone. Also, calcification of other tissue like plaque, they also impact plasma glucose and insulin sensitivity on the way. And it impacts some markers that we’ve talked about multiple times involving inflammation: AMPK, PPAR alpha.

 

Pleiotropic impact of K” –  Insulin Resistance

 

 

So, what we can conclude with this information is that vitamin k  (both k1 and k2) involves anti – inflammatory effects, regulation of adipokine, lipid – lowering effect, calcium effect and insulin sensitivity; If you made it to the bottom of this, I really appreciate it, I’ll keep trying to make this easier to understand for all of us. 

 

 

 

 

References 

  1. J Am Coll Cardiol. 2015 Jun, 65 (23) 2481–2493
  2. https://prevmedhealth.com/coronary-calcium-score-under-utilized-but-still-a-great-test/
  3. https://prevmedhealth.com/vitamin-k2-cardiovascular-health-whats-the-real-score/
  4. https://prevmedhealth.com/vitamin-k2-can-it-remove-plaque/

 

 

 

 

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