I researched vitamin K2 (menaquinone) for my nutrition class last semester, and am excited about sharing what I found with everyone. My intent is just to provide a small overview of everything (none of the ideas are my own – everything is quoted or paraphrased): you can get deeper into research by following links at the bottom. Vitamin K2 has busted out only very recently into research journals, historically overshadowed by its K1 brother which not only is more plentiful in our diets, but whose role in blood clotting factors was a function understood since 1943.^21 Tiny amounts of K2 have been shown to make a significant difference not only in freedom from disease, but in vibrancy and a perfect smile. Sound too good to be true? Researchers have referred to vitamin K2 as "the missing nutrient" and "activator x", but this vitamin is also rightfully referenced as the "sexy factor" (ok that one is my idea): K2 is linked in research I cite below with class 1 occlusion (upper and lower teeth meet where they should with space for third molars), freedom from tooth decay, gorgeous facial structure, strong bones, a sharp mind, fertility, and radiant health.

Researchers believe that it was Vitamin K2 (and specifically the MK-4 isoform of vitamin K2) that Dr. Weston Price was describing in 1939 when he spoke of "a new vitamin-like activator" that worked synergistically with vitamins A and D, which were two other fat-soluble activators that he extensively studied.^1,2,3 In his book, Nutrition and Physical Degeneration, published in 1939, he devoted an entire chapter to K2 (calling it "A New Vitamin-Like Activator"), describing it as a "unrecognized fat-soluble substance that played a fundamental role in the utilization of minerals and whose absence from modern nutrition was responsible for the proliferation of dental caries and other degenerative diseases." ^1,2 Dr Price was a dentist who traveled around the world and studied many different cultures, conclusively finding that dental deformity and tooth decay linearly increased with degree of modernization.

There is extensive literature demonstrating "hunter-gatherers past and present have excellent occlusion, subsistence agriculturalists generally have good occlusion, and the adoption of modern foodways directly causes the crooked teeth, narrow arches and/or crowded third molars (wisdom teeth) that affect the majority of people in industrialized nations."^2 (right picture)

Some researchers "believe this process also affects the development of the rest of the skull, including the face and sinuses"^1,2. Hence, nutrient availability/assimilation influence jaw and tooth development, which directly influence "sexy factor". (the left picture is sexy). The source of these pictures^5 contains a fascinating discussion of populations free from dental decay and dental arch deformity.

Dr. Price took samples of saliva, food, and soil with thousands of pictures, and showed that groups "isolated" from modern influence not only were eating different foods, but the foods they did have in common – vegetables and tubers, for example – contained vastly more nutrients, and were grown in soil which held a nutrient value that was "deliberately maintained"^4

The mystery nutrient was K2

Dr. Price tested samples of dairy products from around the world (by 1945 he had analyzed over 20,000 samples of butter), and found K2 to be present in fish eggs and pasture-raised animals: their fat, organs, and their butterfat products; but only when the animals were "eating rapidly growing green grass…in most regions…the spring and early fall".^1,4 Although Dr. Price was able to quantify the amount of K2 in thousands of samples of dairy products he received from around the world, he couldn't describe its chemical structure, and died before the West heard about research on the vitamin by Russian scientists^1.

There were researchers who took up where Dr. Price left off, and one was Dr. Robert S. Corruccini who serves currently as a professor of anthropology at Southern Illinois University^2 He studied just under 20 cultures: people living industrialized lifestyles all the way to hunter-gatherer lifestyles (he even included samples of some older generations with different lifestyles but the same genes) ^2. His conclusions echoed those of Dr.Price:

maloccclusion (crowded teeth & imperfect bite) is a result of changes in diet and/or lifestyle, is not genetic, and "repeatedly occurs within one or two generations' time" of adopting modern diet/lifestyle^2. There is not a single exception; not a single outlier.

He also demonstrated that wild animals, including nonhuman primates, almost always show perfect occlusion^2. Take home message? Even if it's too late for you, you can still save your children from a gnarly smile and thousands of euro in dental work with tiny amounts of K2. But let's talk about why it's not too late even for you. Let's talk:

Bone density and freedom from disease

1. Vitamins A and D direct cells to make proteins including the two shown on the chart above (under "bones and teeth"): Matrix Gla Protein and Osteocalcin; but K2 is required to activate them once they are made^11. Proteins Gas6 and protein S, which are involved intimately in brain function and the nervous system, also need biological activation by K2.^15

• Osteocalcin protein organizes calcium and phosphorus absorption in the bones and teeth, and K2 supplementation has demonstrated a highly protective effect against bone fractures.^10 Vitamin K2 has a powerful influence on bone-building, and in a completely separate process facilitates a decrease in the bone-loss process^9 Vitamin K2 has been cited as one of the most frequently prescribed treatments for osteoporosis in Japan^9 Notably, in Japan where K2 is given therapeutically for people with bone problems, they describe using enormous doses of K2, up to 45 milligrams per day with no adverse effects observed^9. Can't resist another nod to Dr. Weston Price. Dr. Price ran a series of experiments with chickens that demonstrated that vitamin A and K2 had synergistic effects on mineral absorption of at least calcium and phosphorus^3. He showed young turkeys fed with k2 containing butter along with cod liver oil (A and D) grew at a much faster rate than the unlucky turkeys eating only cod liver oil^3.
• Matrix Gla protein (MGP) is a vitamin K-dependent protein that guards against arterial calcification. Mice lacking MGP "develop heavily calcified aortas and die prematurely".^7 The link between K2 and cardiovascular disease prevention is a very strong one. The Rotterdam Study was a population-based study of 4,600 Dutch men 55 years of age and older, which looked at the association of phylloquinone (K1) and menaquinone (K2) dietary intake "with the incidence of coronary heart disease (CHD), all-cause mortality, and aortic calcification"^6. This study reports food sources of MK-4 as meat and eggs, and sources of MK-5 through MK-10 as fish and fermented produce such as sauerkraut, cheese, and curds^6. Men eating the highest K2 had 51% lower risk of heart attack mortality, 52% lower risk of severe aortic calcification, 41% lower risk of CHD, and 26% lower risk of death from all causes compared to men eating the least K2^6. Lower risk of death from all causes means high intake of K2 doesn't increase the risk for cancer or other major disease: you are less likely to die even from old age!^6 And "there was no consistent association of phylloquinone intake with CHD, mortality, or aortic calcification"^6. Phylloquinone is K1, found in plants: and does nothing to minimize risk factors in this study. Even though the 4,600 Dutch men consumed 10 times more K1 than K2, there was no relationship between K1 and any of those risk factors.^6. The functions of many Gla proteins remain uncertain, but "are suspected to play roles in processes as diverse as bone and cardiovascular mineralization, vascular hemostasis, energy metabolism, immune response, brain metabolism, and in cellular growth, survival, and signaling"^20
• Gas 6 is functionally "involved in a wide range of cellular processes that include cell growth, survival and apoptosis^15. Vitamin K2 also participates in synthesizing sphingolipids, which are in particularly high concentrations in brain cell membranes^15. Brain sphingolipids are responsive to vitamin k2 status, and "are now known to partake in important cellular events such as proliferation, differentiation, senescence and cell-cell interactions"^15. Notably, alterations in sphingolipid metabolism are now linked to neurodegenerative diseases like Alzheimers and Parkinsons^15 Convincing data exists showing vitamin k2 influences cognition and psychomotor behavior^15 Look how clear on this chart nervous system damage is linked to fat-soluble vitamin deficiency! Diseases which disrupt absorption of vitamins have been linked to nervous system issues, and nervous system issues resolve when absorption rates improve, just as we noted in our son ^27

2. K2 protects against vitamin D toxicity. Some researchers believe that "vitamin D exerts toxicity by inducing a deficiency of vitamin K."^12 According to this model:

"vitamin D increases the expression of proteins whose activation depends on vitamin K-mediated carboxylation; as the demand for carboxylation increases, the pool of vitamin K is depleted. Since vitamin K is essential to the nervous system and plays important roles in protecting against bone loss and calcification of the peripheral soft tissues, its deficiency results in the symptoms associated with hypervitaminosis D. This hypothesis is circumstantially supported by the observation that animals deficient in vitamin K or vitamin K-dependent proteins exhibit remarkable similarities to animals fed toxic doses of vitamin D, and the observation that vitamin D and the vitamin K-inhibitor Warfarin have similar toxicity profiles and exert toxicity synergistically when combined. The hypothesis further proposes that vitamin A protects against the toxicity of vitamin D by decreasing the expression of vitamin K-dependent proteins and thereby exerting a vitamin K-sparing effect."^12

So we talked nutrition function and synergy – let's talk......

Structure and Biochemical Individuality. 

My nutrition course tasked us to name specific phases of life when people could particularly benefit from supplementation or increased natural intake, and in the case of K2, I don't know how you could avoid concluding that everyone could benefit in all stages of life from eating natural sources of food with high k2 intake (when defining "high" as at least 32 micrograms). Again, not talking about supplementation of K2 – talking about targeting natural sources of K2. Here are phases I believe I've shown evidence to support so far:

• children wishing to grow normally, have good tooth structure, and maintain health
• anyone pregnant wanting their child to have more "sexy factor". Also, "fetal exposure to warfarin derivatives during the first trimester of pregnancy has long been shown to result in anomalies of the central nervous system…referred to as warfarin embryopathy or fetal warfarin syndrome, includes dilation of the cerebral ventricles, microencephaly, mental retardation, optic atrophy, and blindness"^15 K2 depletion = bad when pregnant.
• nursing mothers wishing to protect their own bones from mineral loss, and wishing to give their infant "sexy factor"
• anyone experiencing or wishing to prevent age-related cognitive decline:
• anyone experiencing or wishing to prevent age-related bone loss

Lifestyle factors that may uniquely benefit from K2 supplementation 

(and of course you would need to consult with your doctor/nutritionist) 

• autoimmunity: All fat-soluble vitamins have potent immunomodulatory properties (meaning they regulate the immune system) so every one can be considered to be therapeutic in autoimmune disease. In fact, quite a few of autoimmune diseases have been linked to fat-soluble vitamin deficiency^16,17. Quite relevant to autoimmune disease, vitamin k2 has antioxidant and anti-inflammatory properties: "emerging data…point to unique actions of…MK-4 against oxidative stress and inflammation"^15
• osteopenia: studies have shown increased bone mineralization with high intake of vitamin K2
• osteoporosis: Japan seems to be ahead of the bell curve on this one: recommending K2 supplementation has been part of their official guideline in treatment of osteoporosis since 1995.^25 And lots of research in support, including meta-analysis of 7 RCTs in 2006 which demonstrated significant decreases in hip, vertebral, & all other fractures following K2 supplementation.^24 K2 supplementation has been shown to not only decrease bone fractures but increase total bone strength and negate loss in vertebral height in the elderly's lower thoracic region.^23 In one study osteoporotic women showed maintenance of bone mineral density even after 2 years with k2 supplementation^9. Vitamin K2 exerts a more powerful influence on bone than vitamin K1, and should be considered for prevention or treatment in those conditions known to contribute to osteoporosis.^9
• Fish eaters: Yes. Vitamin K2 protects neurons from the oxidative damage induced by methylmercury^14. Methylmercury is the predominant form of mercury in fish, and accumulates over time which is why fish at the lower end of the food chain are "safe" and the higher end carry mercury warnings. (Because methylmercury irreversibly binds to selenium, as long as fish have higher levels of selenium than methylmercury, they don't pose a toxin danger)
• Alzheimer's disease. It has been hypothesized based on existing information that chronically low vitamin K1 & k2 are risk factors for Alzheimer's, but the hypothesis needs direct testing to verify^15. Low k1 levels are linked to the ApoE genotype which has long been identified as a risk factor for Alzheimers.^15
• Prostate cancer. Dr. Mercola reported that "Increased intake of vitamin K2 may reduce the risk of prostate cancer by 35 percent, according to the results of European Prospective Investigation into Cancer and Nutrition (EPIC). The potential benefits of K2 were most pronounced for advanced prostate cancer. Vitamin K1 intake did not offer any prostate benefits. The findings were based on data from more than 11,000 men taking part in the EPIC Heidelberg cohort." Here's the abstract but my Library doesn't pull the full text: https://www.ncbi.nlm.nih.gov/pubmed/18400723
• Could k2 also demonstrate a protective effect with breast cancer? This article^19 suggests that might be true, although k2 is so new on the scene it doesn't look as if anyone has formally tested it yet.

Drugs that cause vitamin k deficiency, requiring supplementation:

• warfarin. "Warfarin, a potent vitamin K inhibitor, has demonstrated adverse effects on bone remodeling and atherosclerosis".^26 Rats fed warfarin, a drug that inhibits K2 recycling, develop arterial calcification. Feeding the rats K2 completely inhibits this effect.^14
• Phenytoin. An anti-epileptic drug shown to induce bone loss. K2 supplementation prevented decreased bone mass density^9
• prednisolone. Corticosteroids are known to reduce bone formation and osteoblastic activity^9. Vitamin K2 was able to inhibit reduction of bone calcium content despite patients taking prednisolone^9.

Countries which have more pastured animals offer superior sources of K2. 

There are quality online sources of pastured meat such as https://www.meinbiorind.de/ and https://www.kaufnekuh.de/. But you also don't need to hunt long to find it in the Nuernberg area. Rewe supermarket now offers many different cuts of pastured meat (chicken, pork, and beef) for a reasonable price:

Kerrygold Butter (or any butter from pastured cattle) from Ireland has superior taste, and now you know it's also better for your family's health. Biohof Schwarz (sold at Ebl), as well as Milchbauernhof Kleinlein in Oberasbach offer pastured eggs (but unfortunately not pastured milk). Your purchase of these products supports not only more humane living standards for the animal you're eating, but your own improved health and that of your kids.

Reference List:

1. https://www.westonaprice.org/health-topics/abcs-of-nutrition/on-the-trail-of-the-elusive-x-factor-a-sixty-two-year-old-mystery-finally-solved/ (Feb 2008)

2. https://wholehealthsource.blogspot.de/2009/09/malocclusion-disease-of-civilization.html discusses An epidemiologic transition in dental occlusion in world populations (https://www.ncbi.nlm.nih.gov/pubmed/6594064) which Wahlstrom library doesn't provide in fulltext.

3. https://wholehealthsource.blogspot.de/2008/06/vitamin-k2-menatetrenone-mk-4.html

4. https://www.westonaprice.org/our-blogs/cmasterjohn/the-scientific-approach-of-weston-price-part-3-the-scope-of-prices-work/

5. https://wholehealthsource.blogspot.de/2009/10/malocclusion-disease-of-civilization_10.html

6. Dietary Intake of Menaquinone is Associated with a Reduced Risk of Coronary Heart Disease: The Rotterdam Study (2004) https://jn.nutrition.org.libproxy.bridgeport.edu/content/134/11/3100.full.pdf+html

7. Assay for Human Matrix Gla Protein in Serum: Potential Applications in the Cardiovascular Field https://atvb.ahajournals.org/content/20/5/1257.full

8. Menaquinones, Bacteria, and the Food Supply: The Relevance of Dairy and Fermented Food Products to Vitamin K Requirements https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3941825/

9. Vitamin K2 in bone metabolism and osteoporosis https://eds.a.ebscohost.com.libproxy.bridgeport.edu/ehost/pdfviewer/pdfviewer?sid=d1c414c8-2823-4e56-a40c-05c508fea361%40sessionmgr4002&vid=1&hid=4110

10. Vitamin K and the prevention of fractures: systematic review and meta-analysis of randomized controlled trials. https://www.ncbi.nlm.nih.gov/pubmed/16801507

11. Vitamin K2 Enhances Osteocalcin Accumulation in the Extracellular Matrix of Human Osteoblasts In Vitro https://onlinelibrary.wiley.com.libproxy.bridgeport.edu/doi/10.1359/jbmr.1997.12.3.431/abstract

12. Vitamin D toxicity redefined: vitamin K and the molecular mechanism https://www.sciencedirect.com.libproxy.bridgeport.edu/science/article/pii/S0306987706007171

13. Tissue-specific utilization of menaquinone-4 results in the prevention of arterial calcification in warfarin-treated rats. https://www.ncbi.nlm.nih.gov/pubmed/14654717

14. Vitamin K has the potential to protect neurons from methylmercury-induced cell death In Vitro https://onlinelibrary.wiley.com.libproxy.bridgeport.edu/doi/10.1002/jnr.22630/epdf

15. Vitamin K, an emerging nutrient in brain function https://eds.b.ebscohost.com.libproxy.bridgeport.edu/ehost/pdfviewer/pdfviewer?sid=1844d692-3f0e-4827-8f68-1c74123f1477%40sessionmgr107&vid=1&hid=108

16. Fat-soluble vitamins as disease modulators in multiple sclerosis https://onlinelibrary.wiley.com.libproxy.bridgeport.edu/doi/10.1111/ane.12045/full

17. Overview of general physiologic features and functions of vitamin D https://ajcn.nutrition.org/content/80/6/1689S.full

18. https://articles.mercola.com/sites/articles/archive/2008/05/03/the-vitamin-you-need-to-prevent-prostate-cancer.aspx?source=nl

19. The anticancer effects of vitamin K https://www.cancer.cytoluminator.com/cancer-photodynamic-therapy/vitamin%20k.pdf

20. Recent trends in the metabolism and cell biology of vitamin K with special reference to vitamin K cycling and MK-4 biosynthesis https://www.jlr.org/content/55/3/345

21. Vitamin K Metabolism https://link.springer.com/chapter/10.1007/978-1-4899-1789-8_19

22. Menatetrenone and vitamin D2 with calcium supplements prevent nonvertebral fracture in elderly women with Alzheimer's disease https://www.sciencedirect.com.libproxy.bridgeport.edu/science/article/pii/S8756328204003849

23. Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women https://www.ncbi.nlm.nih.gov/pubmed/23525894

24. Vitamin K and the prevention of fractures: systematic review and meta-analysis of randomized controlled trials https://www.ncbi.nlm.nih.gov/pubmed/16801507

25. Vitamin K2 https://www.ncbi.nlm.nih.gov/pubmed/18830045

26. Vitamin K: Fracture Prevention and Beyond https://www.sciencedirect.com.libproxy.bridgeport.edu/science/article/pii/S1934148211002425

27. Tourette Syndrome and Non-Coeliac Gluten Sensitivity. Clinical Remission with
a Gluten-Free Diet: A Description Case https://www.omicsgroup.org/journals/tourette-syndrome-and-noncoeliac-gluten-sensitivity-clinical-remission-with-a-glutenfree-diet-a-description-case-2167-0277.1000183.pdf