Vitamin K2 MK-4: Dr. Price’s Activator X and Its Transformational Potential

🖨️ Print post

Our inquisitive two-year-old granddaughter, like most children her age, has discovered the word “why.” “Why” is one of the most powerful words in our language. “Why, grandma?” “Why?” She has become aware of the world and has a relentless curiosity to under­stand it. There is no agenda with her “why,” just a strong desire to learn and understand.

When she is given an answer, you can see her digesting the information. She will most likely follow it up with a few more “whys” before she is satisfied. We have to laugh. Sometimes, there isn’t an easy answer to her simple “whys,” but she is learning a very important lesson: Asking the right questions in life leads to understanding.

THE “WHY” THAT BEGAN A GLOBAL QUEST—AND THE MAN WHO ASKED IT

Dr. Weston A. Price was born in 1870 and was raised on a farm in Canada. He had just graduated from dental school and had opened up his first practice when he came down with typhoid fever. Price retreated into the Canadian wilderness, where he ate “milk, fish, and wild berries” to heal himself.¹ As he regained his health, Price noticed that the decay of his teeth had stopped. He began thinking that tooth decay might be tied to health and that nutrition could be key to both dental and overall health.

In 1931, he began a quest to answer the simple but inspirational question, “Why do all my patients have rampant tooth decay?” Price’s research on diet, nutrition and health—sum­marized in his masterful book, Nutrition and Physical Degeneration2—sets him apart from today’s researchers because his work was all based on food, not the synthetics that investiga­tors commonly study now. In fact, he and some of his peers found that any time synthetics were used, there were abnormalities and unwanted calcification throughout the body.

DIET, DISEASE AND DECAY

Along with tooth decay, Price’s patients had narrow nasal passages, resulting in mouth breathing in many children. They also had nar­row faces and palates, leaving inadequate room for teeth. Children living on modern, processed foods were “growing taller, but the bones of the hips were getting narrower, leading to later complications in pregnancy for the girls.”¹ Price called these improper formations “intercepted heredity.”

Dr. Price concluded from his field studies that physical degeneration was a byproduct of modern foods, namely, white flour, sugar, processed oils and other highly refined and processed foods. This was and still is a monu­mental discovery! Other physicians in his time were aware of cultures that had little or no dental decay, but none of them had made the connec­tion between diet, decay and disease.

In short, the problems Price witnessed in his practice came from nutritionally deficient diets. He proved that when modern foods replaced traditional diets full of fat-soluble “activators” (vitamins), dental disease and physical degen­eration occurred.

Surprisingly, this knowledge remains lost or hidden in our modern society. Has your dentist ever told you that you needed to get more grass-fed animal fat in your diet or that you needed more vitamin K2 MK-4?

PRIMITIVE CULTURES AND SOPHISTICATED DIETS

The fourteen different cultures that Price traveled the world to study had strong bodies, beautiful facial symmetry, negligible tooth decay and jaws broad enough to maintain straight teeth even after the wisdom teeth came in. These “primitive” people had a sophisticated understanding of the importance of food and a great respect for the nutritional needs of women and their developing babies. These cultures purposefully handed down their knowledge about food’s importance to future generations to ensure the health of their people and families.

Compared to the Western or modern or Standard American Diet, Price found that the native peoples he studied consumed ten times more of the fat-soluble vitamins. Foods containing these fat-soluble vitamins were especially generous parts of the diet during preconception, preg­nancy, lactation and childhood growth and development, as well as a priority for the elderly.

Nutrient-dense foods, which included lots of healthy animal fats containing fat-soluble activators, maintained the physical integrity of people eating their traditional diets. They had no doctors, dentists or hospitals but instead maintained their health through the careful food choices they made. Fortunately for these cultures, they had no access to the empty calories that are so prevalent in our modern diet.

This ancestral knowledge of nutrient-dense foods is a legacy we need to learn, teach and instill in our children and grandchildren. At no point in our history has it been more imperative. We are living in highly contaminated environ­ments with food-like substances advertised and pushed on us through media, government and school systems from a young age. This carefully coordinated attempt to hook us on white flour, sugar, processed oils and addictive additives is good for the bottom line of big food businesses but horrible for our health.

ACTIVATOR X = VITAMIN K2 MK-4

Price carried out extensive experiments in both animals and humans with a fat-soluble vitamin that he called “Activator X,” which we now accept as vitamin K2 MK-4. (Note: In 2015, the Weston A. Price Foundation sent samples of butter, butter oil and ghee to a lab to test for vitamin K2 content. The only vitamin K2 in these was MK-4. See Table 1)

In one of Price’s experiments, he fed eight groups of rats a deficiency diet with varying amounts of “butter vitamins” (the term he used for his source of vitamin K2 MK-4) or, in two groups, cod liver oil. In his research, he found that the more butter vitamins given to the rats, the better the calcification and development of their bones and joints.³ Table 2 summarizes the amount of butter vitamins (and cod liver oil) given to each group.

From each group, Price chose one rat’s x-rays to summarize the group’s results (See Figure 4). Each group had an x-ray showing the forepaw, wrist, femur and tail. In the original photo from his experiment, you can see the progression of calcification and bone development comparing the eight groups of rats.

The rats in Group 1, the control group, received no butter vitamins or cod liver oil. The decreased bone density was noted and can be seen in the photo on page 33. Several bones are not completely formed or are absent, especially the carpal bones (the small bones that make up the wrist), which are largely missing.

In Group 2, the rats received 0.5 percent of their diet as butter vi­tamins. Even this small amount produced a marked difference in their skeletal development and also increased their bone density. In particular, a large change was noted in the carpal bones, whose formation was more complete. The relation of the epiphyses (the rounded ends or tips of long bones) to the diaphyses (the main or midsection of long bones) is also very easily seen in the bones of the tail.

In Groups 3 and 4, the rats received 1 and 2 percent of their diet, respectively, as butter vitamins. Group 5 rats received 4 percent of their diet as butter vitamins, and Group 6 received 8 percent of their diet as butter vitamins. The photo shows that as the amount of butter vitamins in the diet increased from Groups 2 through 6, the rats displayed an increased bone density.

The rats in Group 7 received 2 percent of their diet as cod liver oil instead of receiving butter vitamins. Cod liver oil is what Price used as his source of vitamin A. This group has several noted structural differences. First, Group 7’s rats have an increased length of the shaft of the bones when compared with Groups 2 through 6 (which only received butter vitamins). Second, the calcification is not as extensive when compared to the Group 6 rats given 8 percent of their diet as butter vitamins. There is better calcification in the butter vitamin group than in the cod liver oil group. At the tail, the epiphyses at their junctions with the diaphysis are more advanced in the closure of the interspace in the cod liver oil group than in the butter vitamin group.

Finally, the Group 8 rats received 2 percent of their diet as butter vitamins and another 2 percent as cod liver oil. Notably, the bones are much larger and the development of the carpal bones are more complete in this group.

As the Group 8 results show, the best calcification and bone devel­opment in this experiment was present when Price used both the butter activators and cod liver oil. Why? Vitamin A, in the cod liver oil, signals the body to make specific proteins, and vitamin K2 MK-4 activates them. Vitamin D also signals the body to make specific proteins activated by vitamin K2 MK-4. Once activated, it directs calcium to where it should be in the body and pulls it from where it should not be.³

Vitamin K2 MK-4 is strongly and directly linked to calcium homeostasis. Calcium is the most abundant mineral in our bodies, with 99 percent of it found in our bones and teeth, and the remaining 1 percent circulating in the blood, muscle and other tissues. Calcium has further importance in the circulatory system and is critical for mediating vascular contraction and vasodilation (the increase in the diameter of blood vessels, which, in turn, decreases blood pressure). Calcium also plays important roles in the brain, nerve transmission, muscles, extracel­lular fluid, intracellular signaling and hormonal secretion. Our bones release calcium for these critical metabolic functions through the process of bone remodeling and calcium homeostasis.

DEFICIENCY AND/OR INSUFFICIENCY

In his practice, Price began using diet and vitamin K2 MK-4 (in the form of butter oil) to prevent and heal cavities, arthritis, rickets, fractures, failure to thrive, heart conditions, rheumatism, learning difficulties and cogni­tion problems.² He especially emphasized the importance of pregnant women getting enough vitamin K2 MK-4 in their diets.

A young boy who had received only dairy products rich in vitamin K2 MK-4 was voted the healthiest child out of forty-one children (see Figure 5).³

Nowadays, it is estimated that 97 percent of people are deficient in vitamin K2 MK-4.4 The best dietary sources of vitamin K2 MK-4 come from animal products.

TWO FORMS OF VITAMIN K

Vitamin K exists in two natural forms, K1 and K2. Vitamin K2 is made of menaquinones (MKs), with MK-4 unique among the MKs as it comes from animal foods. (See Figure 3.) The longer-chain MKs are of bacterial origin. Good sources of vitamin K1 include leafy green vegetables such as collard greens, spinach, kale and broccoli; however, the body absorbs less than 10 percent of vitamin K1 from plants. So, how did cultures living in areas with no leafy green vegetables throughout the year get vitamin K1 in their diet? Can vitamin K2 perform the roles of vitamin K1?

In U.S. hospitals, it is standard practice to administer a vitamin K1 shot to newborns to prevent hemorrhagic disease of the newborn. Some believe newborns do not get sufficient vitamin K1 from their diets until around six months of age when they start eating foods containing vitamin K1. In theory, supplying the newborn with sufficient vitamin K1 will al­low normal blood clotting.

A 1997 study used an oral vitamin K2 supplement (synthetic MK- 4) at a Philippine general hospital, with a sample size of eighty healthy full-term breastfed babies, to determine the efficacy of multiple doses of oral vitamin K2.⁵ When they compared the results of vitamin K2 oral supplementation to those from a single-dose vitamin K1 shot, they found, to their surprise, that oral vitamin K2 supplementation was generally comparable in efficacy to the vitamin K1 shot.

In a 2020 review published in Nutrients, Japanese researchers from the University of Occupational and Environmental Health at Kitakyushu looked at evidence from various countries on how Vitamin K Deficiency Bleeding (VKDB) could be prevented by oral administration of vitamin K2 (MK-4).⁶ The review included consideration of five nationwide sur­veys done in Japan between 1981 and 2004, which showed that giving babies one to three doses of a syrup formulated with vitamin K2 MK-4 reduced late-onset VKDB. Specifically, over the period of twenty-plus years, VKDB in Japan dropped from 10.5 per hundred thousand births in the first survey (1981) to 1.9 per hundred thousand births in the fifth survey (2004). Following the introduction of new guidelines in 2011, the practice of weekly oral supplementation for infants until they are three months old has become common in much of Japan.⁶

In 2012, the Japanese pharmaceutical com­pany Sannova received approval for a vitamin K2 syrup for the prevention of VKDB in neo­nates and infants.

Many studies state that breastfed babies have a higher deficiency of vitamin K2 MK-4 due to low placental transfer and low amounts of vitamin K2 MK-4 in breast milk.⁷ Could this be explained by not having enough vitamin K2 MK-4 in the mother’s diet? After all, developing babies get their nutrition from their mother in the womb. After delivery, they get their nutrition from their mother’s breast milk. If their mother is deficient in vitamin K2, how can she give what she does not have to her baby? Questions lead to understanding.

In Price’s field studies, he never reported any cases of VKDB in children. His studies showed only robust health of babies in these cultures. These issues deserve further research.

VITAMIN K DEPENDENT PROTEINS

Vitamin K dependent proteins (VKDPs) provide life-giving functions for the brain and body. To date, researchers have identified be­tween seventeen and nineteen VKDPs. The in­formation on them is vast; for this reason, we are representing just a summary of this information The first seven VKDPs are involved with coagulation and anti-coagulation. The only VKDPs that use vitamin K1 are the coagulation factors: Factor II, Factor VII, Factor IX and Factor X. The other VKDPs require vitamin K2 MK-4 as a cofactor for the enzyme γ-glutamyl carboxylase (GGCX) to become bioactive. GGCX modifies the glutamic acid residues (Gla) in these proteins, promoting calcium binding and inducing conformational changes.

There are many other functions of vitamin K2 MK-4 outside the activation of the VK­DPs, however. Vitamin K2 MK-4 is present in virtually every tissue, including the brain, heart, bone, sternum, reproductive organs, salivary glands, pancreas, kidney, placenta, vasculature, cartilage, skin, breastmilk, other body organs and cells. Vitamin K2 MK-4 is important for mitochondrial health, protection against oxidative stress, cancer prevention, relief of menopausal symptoms, protection of nerve cells, bone mineralization and protection against arterial calcification.⁸ It is also involved in cellular actions, including nerve transduction, growth regulation, cell migration/chemotaxis, adhesion, apoptosis (programmed cell death), phagocytosis (whereby cells ingest or engulf other cells or particles), senescence, inflamma­tory responses and sphingolipid synthesis,^9-10 but those topics are for another article.

Understanding vitamin K2 MK-4’s multiple roles in prevention and maintenance of our bod­ies grows more important each day, as it directly or indirectly regulates hundreds of physiological and pathological processes.

COAGULATION PROTEINS

Whenever the integrity of a blood vessel is compromised, VKDPs are there to start the healing process of blood clot formation. This is called the “coagulation cascade” and is critical for hemostasis (the stopping of bleeding). As mentioned, these VKDPs include Factor II, Factor VII, Factor IX and Factor X. There are also VKDPs involved in hemostasis that ensure that clotting does not become excessive; these anticoagulant proteins are Protein C, Protein Z and Protein S.

In the intrinsic pathway, a cascade of reactions starts with damage to vessel walls leading to Factor IX being activated.¹¹ This pathway continues on with further reactions and leads into the final common pathway that starts with the activation of Factor X.

The extrinsic pathway starts through a series of reactions involv­ing tissue factor (TF), which is exposed on damaged endothelial cells, activating Factor VII that also leads into the final common pathway.¹²

Once Factor X is activated to Factor Xa (the “a” means it is activated), this protein bridges the gap between the initiation and amplification phas­es of clotting by converting prothrombin into thrombin.¹³ Thrombin then converts fibrinogen into fibrin, and fibrin forms a web of insoluble fibers that trap more platelets and red blood cells, forming a stable blood clot.¹⁴

To ensure that blood clots do not spiral out of control leading to full-body coagulation, anticoagulant proteins are activated. When Protein C is activated by the thrombin-thrombomodulin complex on the surface of endothelial cells lining blood vessels, it joins together with Protein S as its cofactor to inactivate Factor Va and Factor VIIIa.¹⁵ This slows clotting and prevents overproduction of blood clots. Protein Z also slows coagulation as a cofactor to Z-dependent protease inhibitor (ZPI) that inactivates Factor Xa.¹⁶

AUSTRALIAN EMU OIL RICH IN VITAMIN K2 MK-4 AND DR. PRICE’S LEGACY

Price retired from his dental practice in 1943. He then moved to Riv­erside, California, where he continued to lecture and teach people about a lifestyle more in touch with Nature and the foods she provides us. Toward the end of his life, his health was declining and he had taken to his bed, when a friend sent him butter oil rich in vitamin K2 MK-4. He started eating the butter oil and got well enough to get back out of bed and begin lecturing again. Price died in 1948, leaving behind a tremendous legacy.

Through our company, Walkabout Health Products, we have been working with the synergistic power of emu oil that includes vitamin K2 MK-4 for more than a decade, and we have seen how it changes people’s lives. Our emu oil is separate and distinct from other emu oils due to the unrivaled husbandry of the birds. Our latest testing results prove this point. This past year, most of our emu oil has tested at 12,000 ng/g of vitamin K2 MK-4. Our emu oil is a unique source for this vitamin es­sential to life. We believe that Dr. Price would have been in awe of this tremendous resource.

Our ancestors’ DNA evolved with the nourishment of grass-fed animal fats, rich in vitamin K2 MK-4. It kept them free of cavities and gave them strong bones, beautiful faces and healthy hearts. It produced robust men and women who gave birth to healthy, happy children. This is our God-given birthright.

It was not luck that gave us a remarkable inquisitive grandchild; it was proper nutrition with lots of fat-soluble nutrients. Our family is indebted to Dr. Price’s work, to his inspirational “Why” and to the path that asking “why” took him down. We encourage you to read Price’s articles and book, where you can find additional pictures, insights, field studies and conclusions. The knowledge that he gained from his work and travels is a gift to be passed on. Please spread the word.

---

SIDEBAR

OTHER ROLES FOR THE CLOTTING VITAMIN K-DEPENDENT PROTEINS

The role that seven VKDPs—Factor II, Factor VII, Factor IX, Factor X, Protein C, Protein S and Protein Z—play in forming a stable blood clot is by far the most well-known and studied aspect of these proteins. However, further research has revealed that they play further roles in human physiology.

FACTOR II/PROTHROMBIN: Research suggests that prothrombin, specifically thrombin, contributes to cellular func­tions such as cell migration and cell signaling; tissue repair, inflammation and wound healing; and immune responses.¹⁷ Additionally, prothrombin’s activation has been linked to intricate signaling pathways that affect inflammation and gene expression.

FACTOR VII/PROCONVERTIN: Research suggests that this protein may contribute to modulation of inflammatory responses, immune system regulation and the body’s overall homeostasis.^18,19 Additionally, Factor VII is synthesized in the liver, and its levels can be influenced by factors such as diet and certain medical conditions.¹⁹

FACTOR IX/CHRISTMAS FACTOR: A deficiency or dysfunction in this protein leads to a genetic disorder called he­mophilia B, or Christmas disease.²⁰ Individuals with hemophilia B experience prolonged bleeding after injuries and can suffer from spontaneous bleeding into joints and muscles.11 The development of Factor IX replacement therapies has revolutionized the management of hemophilia B, improving the quality of life for those affected by this disorder.

FACTOR X/STUART-PROWER FACTOR: Factor X deficiency can lead to a bleeding disorder known as Stuart-Prower factor deficiency, known for impaired blood clotting and prolonged bleeding after injuries.²¹

PROTEIN C: Research suggests that Protein C may have anti-inflammatory properties, immune modulatory activity, anti-angiogenic activity, anti-apoptotic activity and cytoprotective effects.⁹ Protein C’s protective properties extend to its potential involvement in sepsis. Activated Protein C (APC) has been studied for its potential to mitigate the harm­ful effects of sepsis by counteracting inflammation, improving blood flow and promoting cell survival.²² Protein C is also involved in cell signaling actions in neurons and glia.⁹ In animals, it is neuroprotective in stroke, neonatal hypoxia, brain ischemia, spinal cord ischemia and amyotrophic lateral sclerosis-like diseases.⁹

PROTEIN S: Protein S serves as a modulator of the body’s immune response and inflammation, potentially influencing the activation of white blood cells and the release of inflammatory mediators.23 Protein S is also implicated in processes related to cell growth, apoptosis and tissue repair.24 It has also been known to protect neurons from glutamate-induced toxicity and cell death through the Tyro3-PK3-K-Akt pathway. Vitamin K2 MK-4 also plays a key role in subventricular development during critical neural developmental stages via its control over Protein S availability.²⁵ This is intriguing because subventricular abnormalities are often seen as critical in the development of autism,²⁵ which suggests a po­tential role for vitamin K-dependent processes in developmental brain pathology as seen in cases similar to autism.

Dysfunctional Protein S levels or mutations can lead to increased clotting risk, emphasizing its importance in pre­venting thrombotic disorders.²⁶

PROTEIN Z: Research suggests Protein Z may play a role in modulating inflammatory pathways and even in broader physiological processes. Additionally, Protein Z may be implicated in developing some cardiovascular conditions, although more research is needed to understand this connection fully.

OTHER VITAMIN K DEPENDENT PROTEINS

OSTEOCALCIN (OCN): Involved in bone mineralization and calcium ion regulation, promoting healthy bone forma­tion; crosses the brain-blood barrier, binds to neurons; enhances synthesis of neurotransmitters, prevents anxiety and depression, necessary for brain development and function, spatial learning and memory; insulin release and beta cell protection from high glucose production; testosterone stimulation.

MATRIX Gla PROTEIN (MGP): Helps prevent calcification of vascular, cartilage and other soft tissue calcification. Plays a role in bone organization, protective for the kidney, necessary for proper mid and lower facial development (as described by Dr. Price in Nutrition and Physical Degeneration); contributes to overall cardiovascular health by inhibiting arterial calcification.

Gla-RICH PROTEIN (GRP): GRP is found in cartilage, bone, skin, thyroid and the vascular system; potent inhibitor of calcification of vascular, cartilage and other soft tissue; protective for the kidney.

GROWTH ARREST-SPECIFIC 6 (Gas6): Abundantly expressed in fibroblasts; is involved in cell survival, proliferation and immune response regulation. It is the sole ligand of the AXL tyrosine kinase receptor, Gas6/AXL pathway regulates angiogenesis, immune-related molecular markers, the secretion of certain cytokines in the tumor microenvironment, modulates the functions of a variety of immune cells, role in remyelination.

PERIOSTIN: Acts on a metabolic and genetic level. It is secreted from fibroblasts that make connective tissue; plays a role in repair and remodeling of bone, tooth and heart valves, immune response and wound healing. Important for tissue repair and myocardial remodeling of heart following injury. Expressed in periodontal ligament, placenta, cardiac valve, adrenal gland, embryonic periosteum and thyroid tissue.

TRANSTHYRETIN (TTR): Functions as a carrier protein for thyroid hormones and retinol, contributing to their transport and distribution throughout the body.

PROLINE-RICH GLA PROTEIN 1 (PRG1)

PROLINE-RICH GLA PROTEIN 2 (PRG2)

TRANSMEMBRANE GLA PROTEIN 3 (TMG3)

TRANSMEMBRANE GLA PROTEIN 4 (TMG4)

These four VKDPs are a group of integral membrane Gla proteins; they are found in fetal and adult tissues, and are thought to be involved in diverse cellular functions such as signal transduction, cell cycle progression and protein turnover.

INTER-ALPHA-TRYPSIN INHIBITOR HEAVY CHAIN H2 (ITIH2): Acts as an acute phase protein, that is down- and upregulated, respectively, during an inflammatory response.

It is clear that vitamin K dependent proteins—and hence vitamin K2 itself—are involved in virtually all bodily processes, including building bones and tendons, creating a healthy nervous system, hormone production and protection from cancer. Modern research on vitamin K dependent proteins shows us the folly of avoiding animal fats, organ meats and other nutrient-dense foods. All these life-giving functions and processes depend on having adequate amounts of vitamin K in our diets.

Dr. Price was very concerned for the health of his nieces and nephews. In a letter Dr. Price told them, “One of our greatest struggles is to get sufficient amounts of the vitamins, particularly the fat-soluble vitamins. There is a great ten­dency toward trying to supply these with synthetic products which are not a substitute. The amount of minerals that are in the food that we eat, that will be utilized by the body, will be largely determined by these activating substances.”

For references and further information, visit walkabouthealthproducts.com.

All photographs in this article were provided by the Price-Pottenger Nutrition Foundation.
Copyright Walkabout Health Products.

REFERENCES

1. Johnson K. The pioneer who linked diet and disease: Weston Price DDS. Price-Pottenger Nutrition Founda­tion. (Published in East West Journal, March 1985.) https://price-pottenger.org/research/the-pioneer-who-linked-diet-and-disease-weston-price-dds/
2. Price WA. Nutrition and Physical Degeneration. La Mesa, CA: Price-Pottenger Nutrition Foundation, 2008 (originally published in 1939).
3. Price WA. Control of dental caries and some associated degenerative processes through reinforcement of the diet with special activators. The Journal of the American Dental Association (1922). 1932;19(8):1339-1369. https://doi.org/10.14219/jada.archive.1932.0308 [Read before the Section on Histology, Physiology, Pathology, Bacte­riology and Chemistry (Research) at the Seventy-Third Annual Session of the American Dental Association, Memphis, Tenn., Oct. 20, 1931.]
4. Bruno EJ. The prevalence of vitamin K deficiency /in­sufficiency, and recommendations for increased intake. J Hum Nutr Food Sci. 2016;4(1):1077.
5. Angeles-Melendres, EA., Garcia Jr., EB. Oral vitamin K2 (Kaytwo syrup) for the prophylaxis of hemorrhagic disease of the newborn in healthy breastfed neonates 163. Pediatr Res. 1997; 41:779.
6. Araki S, Shirahata A. Vitamin K deficiency bleeding in infancy. Nutrients. 2020;12(3):780.
7. Shinzawa T, Mura T, Tsunei M, et al. Vitamin K absorp­tion capacity and its association with vitamin K defi­ciency. Arch Pediatr Adolesc Med. 1989;143(6):686-689.
8. Berkner KL, Runge KW. The physiology of vitamin K nutriture and vitamin K-dependent protein function in atherosclerosis. J Thromb Haemost. 2004;2(12):2118- 2132.
9. Ferland G. Vitamin K and brain function. Semin Thromb Hemost. 2013;39(8):849-855.
10. Yan Q, Zhang T, O’Connor C, et al. The biological re­sponses of vitamin K2: a comprehensive review. Food Sci Nutr. 2023;11(4):1634-1656.
11. Orlova NA, Kovnir SV, Vorobiev II, et al. Coagulation factor IX for hemophilia B therapy. Acta Naturae. 2012;4(2):62-73.
12. Mariani G, Bernardi F. Factor VII deficiency. Semin Thromb Hemost. 2009;35(4):400-406.
13. Freedman SJ, Furie BC, Furie B, et al. Structure of the calcium ion-bound gamma-carboxyglutamic acid-rich domain of factor IX. Biochemistry. 1995;34(38):12126-12137.
14. Suttie JW, Jackson CM. Prothrombin structure, activation, and biosynthesis. Physiol Rev. 1977;57(1):1-70.
15. Dahlbäck B, Villoutreix BO. Regulation of blood coagulation by the protein C anticoagulant pathway: novel insights into structure-function relationships and molecular recognition. Arterioscler Thromb Vasc Biol. 2005;25(7):1311-1320.
16. Almawi WY, Al-Shaikh FS, Melemedjian OK, et al. Protein Z, an anticoagulant protein with expanding role in reproductive biology. Reproduction. 2013;146(2):R73-R80.
17. Iannucci J, Renehan W, Grammas P. Thrombin, a mediator of coagulation, inflammation, and neurotoxicity at the neurovascular interface: implications for Alzheimer’s disease. Front Neurosci. 2020;14:762.
18. Kondreddy V, Wang J, Keshava S, et al. Factor VIIa induces anti-inflammatory signaling via EPCR and PAR1. Blood. 2018;131(21):2379-2392.
19. Porreca E, Di Febbo C, di Castelnuovo A, et al. Association of factor VII levels with inflam­matory parameters in hypercholesterolemic patients. Atherosclerosis. 2002;165(1):159-166.
20. Giannelli F. Hemophilia. Encyclopedia of Genetics, 2001, pp. 917-920.
21. Chatterjee T, Philip J, Nair V, et al. Inherited factor X (Stuart-Prower factor) deficiency and its management. Med J Armed Forces India. 2015;71(Suppl 1):S184-S186.
22. Martí-Carvajal AJ, Solà I, Gluud C, et al. Human recombinant protein C for severe sepsis and septic shock in adult and paediatric patients. (Cochrane Database Syst Rev. 2012;12(12):CD004388.
23. Rezende SM, Simmonds RE, Lane DA. Coagulation, inflammation, and apoptosis: different roles for protein S and the protein S–c4b binding protein complex. Blood. 2004;103(4):1192- 1201.
24. Anderson HA, Maylock CA, Williams JA, et al. Serum-derived protein S binds to phos­phatidylserine and stimulates the phagocytosis of apoptotic cells. Nat Immunol. 2003;4(1), 87–91.
25. Ginisty A, Gély-Pernot A, Abaamrane L, et al. Evidence for a subventricular zone neural stem cell phagocytic activity stimulated by the vitamin K-dependent factor protein S. Stem Cells. 2015;33(2):515-525.
26. Gupta A, Tun AMT, Gupta K, et al. Protein S deficiency. Treasure Island, FL: StatPearls Publishing, last updated Dec. 5, 2022. https://www.ncbi.nlm.nih.gov/books/NBK544344/

This article appeared in Wise Traditions in Food, Farming and the Healing Arts, the quarterly journal of the Weston A. Price Foundation, Fall  2023

🖨️ Print post