Thursday, March 31, 2016

3 important ways Vitamin K2 improves gut health

Do you have irritable bowel disease or just overall poor digestion?  Do you feel like inflammation runs rampant throughout your body causing you to be tired and achy all day everyday?  Are you concerned with your exposure to chemicals such as bisphenol-A(BPA)?  Have you been working to fix these problem with dietary changes and supplements with only minor improvement?  Well, there may be a new player in the digestive health scene, but it's actually an old player: Vitamin K2.

Vitamin K2 improves gut health in 3 important ways:

1)It helps improve leaky gut by increasing tight junction proteins
2)It reverses inflammation caused by lipopolysaccharide by changing its structure
3)It promotes the 3 phases of cellular detoxification

These 3 powerful steps can dramatically increase your gut health if you have poor Vitamin K2 intake.  So let's take a look at Vitamin K2 and its role in maintaining gut health.

Dr. Weston A. Price, DDS

The History of Vitamin K2

Vitamin K2, also known as menaquinone, was first identified by Dr. Weston A. Price in his journey to discover the effects of the modern diet on dental and overall health.  In his research, he identified some unknown Activator X found in the butterfat and organs of mammals fed a diet high in grass that had profound effects on dental and overall health.  It seemed that this Activator X was somehow responsible for putting calcium where it was supposed to be, in the bones and teeth, while at the same time removing it from places it shouldn't be, the blood vessel walls.

At the time, Dr. Price didn't know that Activator X was Vitamin K2, he didn't have the sophisticated equipment to determine what was improving the health of his patients, but he knew where to find it and that it worked synergistically with vitamins A and D by activating proteins that these vitamins helped synthesize.  It wasn't until 2008 that Chris Masterjohn was able to put the puzzle together and figure out that Activator X was Vitamin K2 and that animals convert Vitamin K1 in to Vitamin K2 and store it that way.

Once identified as Vitamin K2, research on Activator X started piling up, providing evidence for its positive effect on bone, dental, and cardiovascular health.  The story didn't seem to end there.  There were some interesting findings on the way that raised some serious questions.  The three organs that store the most Vitamin K2 are the pancreas, salivary glands, and brain.  None of these organs are directly related to the proposed effects of Vitamin K2 save for the salivary glands and their effect on dental health, so why do they store Vitamin K2?  It's role in brain health is still undetermined, but we may have an idea as to why it's found in the pancreas.

The pancreas and its outlet in to the duodeunm

Vitamin K2 in the Pancreas

What purpose does storing vitamin K2 serve in the pancreas?  Given the organs function in regulating blood glucose levels, the initial thought was that it had some effect on regulating insulin secretion, and there is evidence that it may have some role there(1).  However, the pancreas also plays a pretty significant role in digestion by secreting digestive enzymes in to the gut to help break down food.

There are multiple forms of Vitamin K2 denoted by the letters MK- followed by a number.  Humans and all animals store Vitamin K2 as MK-4, and as mentioned before the pancreas stores the most.  However, an interesting thing about the MK-4 stored in the pancreas is that it isn't all used in the pancreas, during digestion the pancreas secretes a substantial amount of MK-4 in to the digestive tract via the common bile duct.  This led researchers to believe that Vitamin K2 plays a role in synthesizing, secreting, or activating digestive enzymes(2).  The exact role of Vitamin K2 in digestion remained elusive, however.

A couple of more recent studied looking at the effect of administration of Vitamins K1 and K2 may have clarified some of these roles.  When K1 and K2 were administered to rats, the expression of genes responsible for the synthesis of intestinal alkaline phosphatase(3, 4) and the pregnane X receptor increased(3).  Both of these genes play major roles in regulating inflammation and detoxification in the digestive tract, and through different mechanisms.

Presence and absence of tight junction proteins in the intestine 

Intestinal Alkaline Phosphatase as a Regulator of Gut Mucosal Defense

Many cells throughout the body manufacture alkaline phosphatase, but the primary role of intestinal alkaline phosphatase(IAP) is in gut mucosal defense(5).  In the presence of IAP, the cells that form the intestinal lining increase the expression of tight junction proteins.  This improves the integrity of the intestinal barrier and prevents the contents of the digestive tract from leaking in to the bloodstream.  IAP is also responsible for detoxifying lipopolysaccharide(LPS), a component of the cell wall of gram negative bacteria that induces inflammation.

The human digestive tract contains vast amounts of gram negative bacteria which can cause excessive inflammation if it leaks in to the bloodstream.  When cells of the immune system encounter LPS, it is identified as a foreign invader and causes an increase in inflammation.  IAP changes the structure of LPS, rendering it undetectable to the immune system and reducing inflammation.  IAP is secreted in to the digestive tract throughout the upper small intestine, mixes with the digestive contents, and makes its way through the digestive tract improving tight junction protein expression and detoxifying LPS.  This makes IAP an important regulator of the intestinal immune response.

The 3 phases of cellular detoxification
Note: Phase 3 is the excretion process

The Steroid X Receptor and Detoxification

The Steroid and Xenobiotic Receptor(PXR) also plays a major role in gut health, particularly with regard to detoxification.  The primary function of the SXR is to bind foreign substances and initiate the 3 phases of cellular detoxification responsible for modifying toxins and removing them from the body.  The SXR is responsible for binding chemicals and initiating the metabolism of a variety of toxins, most notable of which is the endocrine disrupting compound bisphenol-A(BPA) ubiquitously found in plastics(6).

When a toxin binds to the SXR, it induces the production of the phase I detoxification enzyme CYP3A4 which modifies it to make it more water soluble.  Next, phase II conjugating enzymes are induced to conjugate the product of phase I, making it readily excretable.  Finally, phase III transport is initiated, removing the toxin completely from the cell and removing it from the body in the sweat, urine or feces.  In the case of the intestine, SXR essentially chews up and spits the toxin back out in to the intestinal lumen, preventing it from entering the bloodstream where it can cause havoc and sending it out the back door.  It performs the same function in the liver which may explain why MK-4 is also stored there.

Healthy gut=Healthy body

Vitamin K2 as a Regulator of Gut Health

There is ample evidence to point to Vitamin K2 as a regulator of gut health.  However, the study identifying its role in upregulation of IAP and SXR expression found both Vitamin K1 and K2 to have these effects in rats.  Vitamin K2 is likely of more significance for two reasons.  First, the study looked at oral supplementation of K1 and K2 which is vastly different than getting either from food. In both studies, K1 had a greater effect in the upper part of the small intestine, and K1 bound to food may not be very bioavailable there(7).  Second, it makes no sense for the pancreas to store and secrete MK-4 in to the duodenum if it isn't serving some purpose in the digestive process, K1 isn't directly involved in this process as far I am aware.

Given the role of the pancreas in the digestive process and the lack of bioavailability of food-based vitamin K1, it appears as though Vitamin K2 may have another role in human health in addition to its better known role in bone, dental, and cardiovascular health.  The role of MK-4 in maintaining gut health may also help explain why supplementing with MK-4 doesn't lead to substantial increases in serum MK-4.  Most of it may be taken up by intestinal cells or recycled to the pancreas from the lymphatic system or portal vein.

One more issue that must be mentioned is the human requirement for Vitamin K2.  To date, there is no differentiation between Vitamin K1 and K2 in terms of what is considered the adequate dietary intake, there is just a general recommendation for the adequate intake(AI) of Vitamin K.  This number is based solely on the amount of Vitamin K required to prevent problems in blood coagulation, it omits the other functions attributed to Vitamin K2 which include bone, dental, cardiovascular, and now gut health.  The rate of conversion of K1 to K2 is estimated to be between 5-25%(7), and if the pancreas requires MK-4 for proper digestive function, an AI of total K based solely on coagulation is far from adequate even if you don't consider its function in bone, teeth and blood vessels.

Gratuitous kitty with a sombrero shot


We are entering a time where the health of the gut is receiving a lot of well-deserved attention for overall health.  Not only is human digestive health on the decline, but many of the diseases that we are succumbing to may be partially attributed to poor digestive health.  Fixing digestive health is no small task, and our current paradigm of throwing acid blocking medications at basically everything is not working.

In the functional medicine realm, probiotics, fiber, magnesium, digestive enzymes, and a host of other nutrients and nutraceuticals have attracted a considerable amount of attention and are used therapeutically to improve nutritional deficiencies and overall gut health.  One nutrient that hasn't received any attention is Vitamin K2.  There is ample evidence to consider Vitamin K2 as a potent modulator of gut health as well as your overall health and well-being.