12 Jun In Defense of Vitamin K2 MK-4: Dr. Price’s Activator X
By Elizabeth Schlinsog and Will Schlinsog, DC
This article is copyrighted by Walkabout Health Products LLC, 2020
The discovery of vitamin K was worthy of the prestigious Nobel Prize in Medicine. In 1943 Carl Peter Henrik Dam, for his discovery of Vitamin K, shared this honor with Edward A. Doisy, for his discovery of its chemical structure.
In 1929 Dam had found that chicks fed a cholesterol-free diet developed a bleeding disorder, not remedied by cholesterol. (He cured them by giving them either green leaves or hog liver.)
He believed that vitamin K was only involved in coagulation. In fact, at the end of his Nobel lecture, Dam stated, “It therefore seems unlikely that vitamin K as such should play any role in the prevention of caries.” 1
Ironically, Dr. Weston A. Price, around the same time, had found a fat-soluble vitamin that he referred to as activator X, which not only helped prevent and heal caries, but also helped shape the very faces of the isolated peoples he studied. He felt it was such an important nutrient that in 1945 he added a new chapter to his book, Nutrition and Physical Degeneration.2
THE K FAMILY
Vitamin K comes in several forms:
1. Vitamin K1 (phylloquinone) is found in plants and some animal sources; it is involved in coagulation.
2. Vitamin K2 has side chains that contain from four to thirteen “isoprenoids,” represented as MK-4 to MK-13. MK means menaquinone; the side chains are referred to as short- and long-chain menaquinones (MKs). Vitamin K2 MK-5 through MK-13 are forms produced by bacterial synthesis.
3. Vitamin K2 MK-4 is Dr. Price’s activator X and is unique, in that it is the only form that is not the product of bacterial synthesis, but comes from animal sources. (A synthetic MK-4 is made from tobacco or geranium leaves.)
4. Vitamin K3 (menadione) is synthetic and water-soluble, and it has no side chain. The FDA banned its use for human consumption because of its high toxicity—although it still is allowed in animal feed, usually as menadione sodium bisulfate (a good reason to eat grass-fed animal products).
5. Menaquinone-7 (MK-7), is an example of a longer-chain menaquinone made by bacterial synthesis; MK-7 is found in natto and supplements.
Dr. Price’s Activator X is vitamin K2 MK-4. Price’s work in nutrition may be more valuable to us today, as it is a place to refer to when the noise of synthetic supplementation drowns out the wisdom of our ancestors – the knowledge that all health starts with nutrient dense, whole foods.
“People of the past obtained a substance that modern generations do not have.”
~ Dr. Weston A. Price
Yet increasingly we are seeing statements in published papers that “it is unlikely that MK-4 is an important dietary source of vitamin K in food supplies.” Such assertions, often by those with ties to the supplement industry, have led us to the defense of this key nutrient in food.
In his studies, Price found a fat-soluble vitamin he called activator X. He believed it was a missing nutrient in our modern diet and that its absence could explain many of our modern diseases. He was able to heal caries, reduce oral bacteria and cure other degenerative maladies in his patients by giving butter oil, rich in activator X, along with cod liver oil. (Cod liver alone did not work as well.)
Price wrote: “(a) [Activator X] plays an essential role in the maximum utilization of body-building minerals and tissue components; (b) its presence can be demonstrated readily in the butterfat of milk of mammals, the eggs of fishes and the organs and fats of animals; (c) it has been found in highest concentration in the milk of several species, varying with the nutrition of the animal; and (d) it is synthesized by the mammary glands and plays an important role in infant growth and also in reproduction.”2
Price found higher levels of vitamin K2 MK-4 in the milk of cows eating rapidly growing green grass. Vitamin K2 MK-4 is concentrated in butter and Price found he could concentrate the amounts further by using centrifugal force in the process, which he called high-vitamin butter oil. He found that the content of vitamin K2 MK-4 varied with the species of the cow, the time of year and the quality of what the cows ate. (See Table 1.)
Note that butter and concentrated butter products contain 100 percent MK-4. (See Table 2.) There are no bacterial MK’s in these products. This is the fat in nature designed for the growth and nourishment of all mammals.
For thousands of years our ancestors had their vitamin K needs met by eating animal sourced foods, foods deemed particularly important for having healthy children.
DEFICIENCY IS PREVALENT
There are many reasons for the modern widespread deficiency of vitamin K2 MK-4: our aversion to eating offal, animals raised eating anything other than grass, factory farms, high antibiotic use in animal feeds and in humans, animals fed GMO corn and soy, soil depletion, glyphosate, processed foods and dysfunction of the gut. If you are taking a statin or blood thinner, you should know these drugs create a deficiency in vitamin K2. Our elderly ancestors ate more of this nutrient as they aged.
How can you tell if you are deficient in vitamin K2? Vitamin K2 MK-4 is important for calcium homeostasis, so if you have osteoporosis, cardiovascular or coronary disease, kidney disorders, diabetes or cancer, it may be due to a deficiency of this nutrient. Tooth decay is another sign of vitamin K2 deficiency. Children brought up on diets lacking in K2 MK-4, starting in the womb, tend to have narrow faces and crowded and crooked teeth.
Cheese contains vitamin K2 MK-4 as well as longer-chain MKs. Cheese is made by adding different bacterial cultures to milk, each one producing a different effect. Typically the MKs found in cheese from the greatest amounts to the least amounts are MK-9, MK-4, MK-8, MK-10, and MK-7. Some cheeses, such as mozzarella or comte, have no short or long MKs. Some cheese aged for ninety to one hundred eighty days may only have vitamin K2 MK-4. Not all fermentation processes or bacteria make long chain MKs.
A study testing eighty-four different foods found that most foods contain small amounts of vitamin K2 MK-4. Rarely do longer chain MKs exist in the meat of chicken, beef or pork. In offal small to moderate amounts of MK-6 to MK-10 have been detected. Fish typically have small amounts of vitamin K2 MK-4.8
Vitamin K2 MK-4 from animal foods is quickly absorbed in the body and is stored in the brain, salivary glands, testes, sternum, face, pancreas, eyes, kidneys, bones, arteries, veins, and other tissues, where it is utilized for activating vitamin K-dependent proteins (VKDP) and possibly for other, as yet unidentified, functions.9
Unlike MK-4, MK-7 is not stored in any organs.
VITAMIN K1 VERSUS VITAMIN K2
There are many forms of vitamin K, and the inclination of articles and studies to refer to all Ks using the term vitamin K or K2 has lead, incorrectly, to the assumption that all Ks are similar in origin and function. They are not.
Many studies state that the main source of vitamin K2 MK-4 is from K1, which we get from green leafy vegetables or vegetable oils, but our bodies absorb miniscule amounts-less than 10%-of K1 from plant foods, and our MK-4 needs are greater than anything we could convert from vitamin K1.10
In 1964, Carl Martius, using pigeons, chickens and rats, was the first to state that MK-4 was made from K1 and he was right-when you are using pigeons, chickens and rats. These animals have gizzards and extra-large, large intestines that can convert K1 to vitamin K2 MK-4.11, 12
Cows, sheep, pigs, chickens and other animals can also make the conversion from K1 to MK-4, but humans, higher up on the food chain, have a digestive system adapted to having our vitamin K2 MK-4 needs met predominantly from eating grass-fed or pastured animals and products made from them. Humans are not fermentative beings. And of course, many ancestral cultures would not have access to greens throughout the entire year and would have obtained their fat-soluble vitamins from animal foods.
Another theory is that we can meet all our vitamin K2 MK-4 needs from bacterial synthesis in the gut, but this premise is not sustained by the evidence. Our gut bacteria can make short- and long- chain MK’s (for their own use), but they do not produce vitamin K2 MK-4. 13, 14, 15
The bio-availability of bacterial MKs is poor because they are tightly bound to the bacterial cytoplasmic membrane, and the largest pool is present in the colon, which lacks bile salts for their solubilization.
Natto, a fermented soy product, is the only food with high amounts of vitamin K2 MK-7–it is an anomaly. It originates from the eastern part of Japan but has not been in most of the world’s diet except in trace amounts. And the Japanese traditionally eat egg yolks, a source of MK-4, with natto.
Interestingly, practitioners in Japan give 45 mg of MK-4 (the synthetic form), not MK-7, to treat osteoporosis.
EVOLUTION AT WORK
In 1988 a Japanese study done by Dr. Hidekazu Hiraike divided pregnant women into two groups, Group A was asked to eat a normal diet and Group B was asked to eat a diet high in natto. Vitamins K1, K2 MK-4, MK-6 and MK-7 were found in the placentas and mothers’ blood plasma.16 (See Table 3.) Samples were taken of the placentas and umbilical cord plasma right after delivery.
Only K1 and MK-4 were found in the umbilical cord plasma, even though there were high concentrations of MK-7 available. It appeared that the placental tissues effectively blocked the passage of MK-7 while allowing MK-4 into the unborn child. High concentrations of Vitamin K2 MK-4 were found in the placenta. 16
MK-7 scientists say that MK-7 is more bio-available or has a longer half-life because it remains in the blood plasma longer than MK-4. However, the Japanese natto study is a living account of nature’s selection for the type vitamin K2 needed for the development of the child–that is, the animal form MK-4. It’s worth hypothesizing that MK-7 may remain in the blood longer because the body has no use for it.
Some studies indicate that MK-7 from food and synthetics induces more complete carboxylation of osteocalcin, a vitamin K-dependent protein involved in bone homeostasis. One study involving menopausal women taking MK-7 as natto over one year showed reduced serum levels of uncarboxylated osteocalcin (ucOC), but the treatment had no effect on bone loss rates.17 Could MK-7 increase the carboxylation of calcium, and yet, lack the ability to move it into the tissues? Could this increase in carboxylation increase the calcification of the placenta or form excess osteocalcin, which does cross into the placenta, causing a decrease in the blood supply (thus less oxygen) and explain the findings of small for gestational age and other defects in the natto study?
In 1992, Dr. Hideaki Iioka found that vitamin K2 MK-4 is transported into the placenta by a carrier protein via an existing transport carrier system in the brush border membrane of the human placenta.18, 19 20. Vitamins A, D, and E are also carried in the blood by a carrier protein. Could this be the reason that vitamin K2 MK-4 is often not detected in the blood, because it is attached to a carrier protein? Little to no research has been done to answer these questions.
What we do know is that the traditional sacred foods for preconception and pregnancy were foods rich in MK-4, and that traditional weaning foods for babies were poultry liver and egg yolks, also great sources of vitamin K2 MK-4.
It’s important to understand that vitamin K2 MK-4 and long chain MKs are structurally different and are derived from different sources.
Some researchers have suggested a theory of conversion from vitamin K1, MK-7, or other MK’s to vitamin K2 MK-4 via the enzyme UBIAD1, which removes the longer side chains of the K vitamins to produce menadione (K3). K3 then travels to the liver for detoxification and is somehow transported in the blood or lymph by an unexplained carrier to tissues where an unknown enzyme(s) adds side chains back to K3 producing vitamin K2 MK-4. 21
The question is, what happens if K3 exceeds the rate at which the enzyme can add back the side chains, as when someone is taking K3 as a supplement? Does the excess K3 cause toxicity and oxidative stress? The research is unclear.
What we do know is that K3 causes disruption or rupture of red blood cells, toxic reactions in liver cells, and depletion of glutathione; it weakens the immune system and can cause allergic reactions.22 The potential for these negative effects is the reason the FDA banned K3 for human use.
The research points strongly to the conclusion that humans need to get their vitamin K2 as MK-4 from food sources. After all, we evolved eating vitamin K2 MK-4. It is already in the form that the body needs, and we don’t need to expend enzymes and energy to convert it. The organs and cells that need vitamin K2 readily absorb and utilize the MK-4 form. And finally, MK-4 is more efficient than other forms, appearing in food with other synergists and activators that work together to maintain therapeutic aspects.
It can’t be stressed enough that the type of vitamin K2 that we get in supplements is MK-7, not the type we get in food. The best way to get active and efficiently assimilated vitamin K2 is from food. This is true of all vitamins. An NIH-funded study involving twenty-seven thousand people over a six-year period found that “individuals who reported taking dietary supplements had about the same risk of dying as those who got their nutrients through food. What’s more, the mortality benefits associated with adequate intake of vitamin A, vitamin K, magnesium, zinc, and copper were limited to food consumption.”23
TAIL SIZE MATTERS
Vitamin K-dependent proteins (VKDP) are a group of proteins providing life-giving functions for the brain and body. To become bio-active they require vitamins K1 and K2 MK-4 as cofactors for the enzyme y-carboxyglutamyl carboxylase (GGCX), which transforms the glutamic acid residues (GLA) in the protein, promoting calcium-binding and inducing conformational changes so that vitamin K can be utilized by the tissues. In other words, vitamin K2 MK-4 is multifunctional.
Once GGCX is activated, vitamin K transforms into the epoxide state; then it is recycled to the quinone and hydroquinone states by vitamin K epoxide reductase (VKORC1).
In 2018, Nolan Chatron and his group used in silico (biological modeling performed on a computer) and in vitro assays for confirmation, using vitamin K1, vitamin K2 MK-4, MK-7 and K3 to give us some insight into tissue distribution and interactions toward VKORC1.24
VKORC1 was shown to tightly bind with vitamins K1 and K2 MK-4. However, MK-7 showed “shaky binding, induced by hydrophobic tail interactions with the membrane.” K3, without a tail, had no structural stabilization by the enzyme. The in vitro assays validated the in silico predictions.
All states of MK-4 exhibited stable values. K1 epoxide and quinone remained inside the VKORC1 enzyme and did not interact with the membrane, although K1 was not as stable in the hydroquinone state. MK-7 showed the highest fluctuations leading to MK-7 binding failure. In vitro MK-7 showed weak activity and was ten times lower than vitamin K1 epoxide; these results were in line with the in silico prediction. K3 in vitro had no activity. (See Figure 2.)
Figure 2 (see below).
Binding free energy of vitamins K (K1, vitamin K2 MK-4, MK-7, and K3 in their epoxide, quinone, and hydroquinone states) towards vitamin K epoxide reductase (VKORC1) and membrane in molecular dynamics (MD) simulations. The binding free energy (BFE) between vitamin K and membrane is shown as black line. The BFEs between the epoxide state of vitamin K and VKORC1 are shown as green, cyan, orange, and red lines for vitamin K1, vitamin K2 MK-4, MK-7, and K3, respectively. The BFEs of quinone and hydroquinone states of vitamins K towards VKORC1 are presented as violet and pink lines, respectively. Two 100-ns MD simulations were performed on each vitamin K–VKORC1 complex, then concatenated to be considered as one 200-ns MD simulation.
In conclusion, the researchers showed the ability of VKORC1 to reduce vitamins K1 and MK-4 for use in the body, but not MK-7 and K3. These findings explained the ability of VKORC1 to support VKPD activation in the liver (mainly containing phylloquinone, vitamin K1), and in extrahepatic tissues (mainly containing vitamin K2 MK-4).
These results led the researchers to ask the question: “Are long-sized hydrophobic tail menaquinones able to act as GGCX cofactors?”
The shorter MKs, K1 and MK-4, were stable, while the longer-chain MKs, such as MK-7 were not able to bind well, and K3 with no tail could not bind at all. Tail length does matter!
Could it be that MK-7 remains in the blood longer because it does not bind well?
NATURE IS WISER THAN ANY HUMAN DESIGN
In 2011, we contacted the Weston A. Price Foundation. We had already been working with emu oil in Will’s practice for a few years with excellent results. The Foundation asked whether we had ever tested our emu oil for vitamin K2. We had never heard of vitamin K2! The results put us on the path of a serendipitous journey.
Emu oil is a whole food with a unique synergy of nutrients; it is the highest naturally occurring source of vitamin K2 MK-4. Emu oil is an ancestral food and bush medicine of the indigenous Australians.
The beneficial properties have long been known to the Aboriginals to reduce pain and inflammation, with documentation recorded more than one hundred years ago.25, 26
Just as Dr. Price found the amount of Activator X (vitamin K2 MK-4) varies with the species of cow and what it eats, these same facts apply to emus. Not all emu oils have the same benefits or characteristics. Genetics, feed, husbandry and refining are all huge components to having the most biologically active emu oil. Testing on two American emu oils detected no vitamin K2 MK-4.
Weston Price has left us a tremendous legacy: the collective knowledge of thousands of years of ancestral wisdom and instinct as a guide to maintaining bountiful, joyful health, generation after generation.
Elizabeth and Dr. Will Schlinsog are the owners of Walkabout Health Products, the exclusive distributors of a unique emu oil, found only on select farms in Australia. Dr. Schlinsog is a chiropractor who has been in practice for over thirty years. He maintains a private practice in Marshfield, Wisconsin. He is trained in disability evaluations, functional medicine, applied kinesiology and functional neurology. He also conducts educational lectures and podcasts regarding the clinical studies and trials using Walkabout Emu Oil as a vitamin K2 MK-4 whole food source. The Schlinsogs feel blessed to work with the farmers in Australia and to bring this resource to their clients. They are grateful to the researchers, fat-soluble experts, nutritionists, holistic doctors, farmers and the people taking their oil who have shared their experiences with it. If you would like to share your experience or learn more about this vitamin K2 MK-4 resource, call (715) 305-2526 or visit walkabouthealthproducts.com.