The K Vitamins:
Vitamin K1 (Phyloquinone) fat soluble from plant tissue
Vitamin K2 (Menaquinone-4) fat soluble, from animal tissue
Vitamin K2 (Menaquinone-7) synthesised by intestinal bacteria and in fermented foods
Vitamin K3 (Menadione) water soluble, most potent form but not found naturally
Vitamin K4 (synthetic)
Vitamin K5 (synthetic)
Vitamin K is best known for its role in helping blood to clot (coagulate) properly; the ‘K’ comes from its German name, ‘Koagulations vitamin’.(1)
Vitamin K is a quinone used in plants in photosynthesis (a phylloquinone). Animals use it for a different purpose.
A sufficient intake of vitamin K is important as it helps the body to:
Clot (i.e. coagulate) blood.
Maintain bone health.
Keep blood vessels functioning optimally.
Modulates the immune system.(2)
Vitamin K1 – The best-known function of vitamin K1 in animals is as a cofactor in the formation of coagulation factors II (prothrombin), VII, IX, and X by the liver. It is also required for the formation of anticoagulant factors protein C and S. It is commonly used to treat warfarin toxicity.(3)
Vitamin K2 – or menaquinone has nine related compounds, generally subdivided into the short-chain menaquinones (with MK-4 as the most important member) and the long-chain menaquinones, of which MK-7, MK-8 and MK-9 are nutritionally the most recognized. Interest in K2 stems from its role in regulating calcium. K2 activates osteocalcin proteins which incorporate calcium into bone. Bone mass acquired through childhood and adolescence leads to healthy bones later in life, which are needed to sustain physical stress and avoid diseases including osteoporosis and osteopenia. Bone mass declines throughout adult life, with peak bone mass (PBM) achieved in childhood at the age of 13 to 19 years. A 10% increase in PBM is estimated to reduce the risk of osteoporotic fracture as we age by 50%. Vitamin K2 also activates matrix GLA (MGP) protein which binds excess calcium to prevent deposit in soft tissues such as arteries, a significant risk factor in cardiovascular disease and a common condition as we age. Vitamin K2 is deficient in the western diet, and, as such, supplementation is critical to good health. The MK-7 form of K2 is optimal for dietary supplementation because it has a half-life of two to three days, compared to the one to two hours of MK-4.
Basically there is an enzyme that takes vitamin K and takes a protein that’s been already made, and converts the glutamic acid to a γ-carboxy glutamic acid (Gla.).4 Glutamic acid has one carboxyl group at the end, and what this does is add another carboxyl group right next door. So you have two carboxyl groups and they combine to calcium. All the proteins that have a Gla in it are calcium-binding proteins, and that’s important in their function. To do that step, Vitamin K2 is required.(4)
Glutamic acid has one carboxyl group at the end, and what this does is add another carboxyl group right next door. So you have two carboxyl groups and they combine to calcium. All the proteins that have a Gla in it are calcium-binding proteins, and that’s important in their function. To do that step, Vitamin K2 is required.(5) Dr. Bruce Ames and Dr. McCann* evaluated the relative lethality of 11 known mouse knockout mutants that are associated with these vitamin K-related proteins. Vitamin K is required for coagulation, so there is something about the blood coagulation matrix that has been very clearly understood. But the priority is to get the essential one for survival, which are the coagulation proteins, and you do that first in the liver, and then only if you have enough do you ship it out to the peripheral regions. Take the matrix Gla protein (Gla stands for γ-carboxy glutamic acid). They also point out that recommended intakes of vitamin K are based on amounts required to maintain coagulation function, not to promote proper enzyme function or gene expression patterns that associated with vitamin K sufficiency. (6)
Vitamin K dependant enzymes
Several human Gla-containing proteins have been discovered:
1. Coagulation factors (II, VII, IX, X), as well as anticoagulation proteins (C, S, Z). These Gla-proteins are synthesized in the liver and play an important role in blood homeo-stasis.
2. Osteocalcin. This non-collagenous protein is secreted by osteoblasts and plays an essential role in the formation of mineral in bone.
3. Matrix gla protein (MGP). This calcification inhibitory protein is found in numerous body tissues, most pronounced in cartilage and in arterial vessel walls. Vitamin K2 is the cofactor for an enzyme called vitamin K dependent carboxylase. This enzyme when activated by K2 alters the structure of osteocalcin and MGP to allow those proteins to bind calcium.
4. Growth arrest-specific protein 6 (GAS6). GAS6 is secreted by leucocytes and endothelial cells in response to injury and helps in cell survival, proliferation, migration, and adhesion.
5. Proline-rich Gla-proteins (PRGP), transmembrane Gla-proteins (TMG), Gla-rich protein (GRP) and periostin; whose precise functions are still unexplored.
Vitamin K and the Immune System – Complex signalling and communication mechanisms at the cellular/molecular level are at the heart of the immune response. Vitamin K2 is a critical component that is required for both the activation and regulation of much of the cellular machinery responsible for initiating and executing our immune response. Vitamin K2 can act as a cofactor for some plasma proteins, thereby affecting immune and inflammatory responses particularly mediated by T cells. Studies have found links between vitamin K levels and diseases, including inflammatory diseases and cancer.(7)
There is evidence that vitamin K can regulate the activation of the NF-κB pathway.
Other cell and animal experiments have looked at the possible regulation of inflammation by vitamin K inhibition of IL-6 release following endotoxin challenge. These researchers also found that Menadione (Vitamin K3) was capable of suppressing LPS-induced NF-κB nuclear translocation and TNF-α release from murine macrophage-like RAW 264 cells. Additionally, in a murine model of acute lung injury/acute respiratory distress syndrome (ARDS), which occurs in the setting of acute severe illness complicated by systemic inflammation, Menadione also attenuated the LPS-induced severity of lung injury and suppressed the increase in serum TNF-α level. This occurred concomitantly with inhibition the LPS-evoked nuclear translocation of NF-κB in lung tissue. (8)
Examination of the effects of Vitamin K3 and Vitamin K5 on proliferation, apoptosis, cytokine production, and CD4+CD25+Foxp3 + regulatory T (Treg) cell-frequency in human peripheral blood mononuclear cells (PBMCs) activated by T cell mitogen in vitro.(9)
Natural sources found in the diet can include any of the following:
Sources K1 Green vegetables (e.g., broccoli, kale, spinach, turnip greens, collards, Swiss chard, mustard greens)
Sources K2 Animal livers especially Goose, Natto, Soft cheese e.g. Camembert, Brie, Gouda, Edam, Sauerkraut. Emu oil, Butter. (10)
Taking Vitamin K2 is contraindicated when taking anticoagulant medication such as Warfarin for thinning the blood in conditions like atrial fibrillation.
1 “Vitamin K”. Micronutrient Information Centre, Linus Pauling Institute, Oregon State University, Corvallis, OR. July 2014. Retrieved 20 March 2017.
2 “Vitamin K”. Micronutrient Information Centre, Linus Pauling Institute, Oregon State University, Corvallis, OR. July 2014. Retrieved 20 March 2017.
3. Ageno, W; Gallus, AS; Wittkowsky, A; Crowther, M; Hylek, EM; Palareti, G; American College of Chest, Physicians. (February 2012). “Oral anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines”. Chest. 141 (2 Suppl): e44S–88S
4. McCann JC, Ames BN. Vitamin K, an example of triage theory: is micronutrient inadequacy linked to diseases of aging? Am J Clin Nutr. 2009;90(4):889-907.
5. American Journal of Clinical Nutrition page 889 or 2009 issue.
6. Jeff Bland Functional Medicine Update April 2010 interviewing Bruce Ames
7. Vitamin K and the Immune System. Nazli Namazi, Bagher Larijani, Leila Azadbakht.ChapterFirst Online: 31 July 2019
8. Anti-Inflammatory Actions of Vitamin K. Stephen J. Hodges, Andrew A. Pitsillides, Lars M. Ytrebø and Robin Soper
9. Effects of vitamin K3 and K5 on proliferation, cytokine production, and regulatory T cell-frequency in human peripheral-blood mononuclear cells HiroshigeHatanaka, HitomiIshizawaYurieNakamura,HirokoTadokoroSachiko,TanakaKenji,OndaKentaro, SugiyamaToshihikoHirano