What is Vitamin K?
Vitamin K is a name given to a group of fat-soluble vitamins which are considered essential cofactors in humans for the production of various proteins involved in coagulation homeostasis and calcium homeostasis. These vitamins include: vitamin K1, K2 (MK-4), K2 (MK-7), and K3. The original term vitamin “K” comes from the letter “K” in the word “Koagulation” meaning the ability to clot blood and prevent haemorrhage. This particular function is associated with vitamin K1.
Vitamin K1 converts protein bound glutamate residues into carboxyl glutamate (GLa) by serving as a cofactor for carboxylation (Schwalfenberg, 2017). Carboxyl glutamate (GLa) containing proteins are found in the blood clotting factors II, VII, IX, and X which are important for blood clot.
Vitamins K2 (MK-4) and K2 (MK-7) are involved in calcium transport by preventing calcium deposition in the lining of blood vessel walls, and have crucial role in improving bone density. The difference between these two forms is that K2 (MK-4) is a short chain form with shorter half-life and K2 (MK-7) is a long chain form with longer half-life. Vitamin K3 is a synthetic analogue of vitamin K and is presently being studied as a potential prostate/hepatocellular cancer therapy and treatment for skin toxicities, secondary to kinase inhibitor therapy (Schwalfenberg, 2017).
Food sources of vitamin K1 are boiled spinach, cooked broccoli and asparagus, red and green grapes, plums, kidney beans, mayonnaise and margarine. Vitamins K2 on the other hand can be found in hard and soft cheeses, egg yolk, butter, chicken, beef, fermented milk and soya. The daily recommended requirement for vitamin K is 90 μg daily for women and 120 μg daily for men (Otten et al., 2008). Deficiency of vitamin K1 is rare, except in new-borns, if present later in life is identified by measuring levels of uncarboxylated GLa proteins. An indicator of vitamin K2 deficiency is the level of uncarboxylated osteocalcin which is also considered as a marker for hip fracture risk (Szulc et al., 1996).
Scientific research over the past few years has pointed towards the importance of K vitamins in osteoporosis, vascular calcification, osteoarthritis, diabetes and cognition.
Vitamin K2 and Osteoporosis
Vitamin K is essential for good bone health due to its ability to improve bone density. Vitamin K2 (MK-7) from fermented soybeans stimulates osteoblasts (cells that make bones) and inhibits osteoclasts (cells that break down bone tissue), resulting in an anabolic effect on bone calcification (Yamaguchi, 2006). In clinical studies, vitamin K2 has been demonstrated effective in maintaining lumbar bone mineral density (BMD). Iwamoto et al. (2004) demonstrated an ability of vitamin K2 to reduce age-related osteoporotic fractures, reduce glucocorticoid-induced osteoporotic vertebral fractures, and maintain lumbar bone mineral density in osteoporotic patients.
Vitamin K2 and Cardiovascular Disease
Vitamin K2 plays an important role in the prevention and reversal of arterial hardening. Excess calcium in the body can be deposited in arteries and vessels in the form of calcium plaques. This is a big risk factor for the development of cardiovascular disease. Vitamin K2 activates osteocalcin enzymes which incorporate calcium into bones. Vitamin K2 (MK-7) has the added benefit of activating a second enzyme which plays a vital role in the circulatory system. Vitamin K2 is essential for the activation of matrix Gla protein (MGP), which is a calcium binding protein. After being activated MGP binds excess, free floating calcium in the blood and prevents it from being deposited in the circulatory system (Cranenburg et al., 2010). High levels of non-activated MGP in the blood are correlated with low vitamin K status and vascular calcification. Studies have shown that K2 supplementation produces a significant decrease in non-activated MGP in healthy adults (Cranenburg et al., 2010; Theuwissen et al., 2012).
Vitamin K2 and Diabetes
Vitamin K supplementation has a potential as a novel adjuvant therapy to improve glycaemic control and quality of life. Deficiency in vitamin K could result in excessive insulin release and reduced clearance of glucose from the blood. A recent placebo controlled trial showed that vitamin K2 supplementation can increase insulin sensitivity in healthy young men via osteocalcin metabolism (Choi et al., 2011). Another study done by Li et al. (2017) suggested further the anti-diabetic function of vitamin K2 by demonstrating its anti-inflammatory and lipid-lowering effects, including its ability to suppress inflammation by inactivating NF-κB signalling pathway.
Vitamin K1 and Cognition
Vitamin K has a significant role in the synthesis of sphingolipids in the brain. More recently, vitamin K dependent proteins such as Protein Gas6 have been shown to play a key role in the peripheral and central nervous system (Ferland, 2012). Vitamin K1 levels in those with Alzheimer’s disease are significantly low. Recent research points out towards the beneficial effect of vitamin K in improving cognitive function. One such study showed that vitamin K1 was associated with better verbal episodic memory performances especially on recall tasks, in healthy older adults (Presse et al., 2013).
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Choi, H., Kim, S.W. et al. (2011). Vitamin K2 supplementation improves insulin sensitivity via osteocalcin metabolism: a placebo-controlled trial. Diabetes Care. 34 (9), 147-151.
Cranenburg, E.C. et al. (2010). Characterisation and potential diagnostic value of cisculating matrix Gla protein (MGP) species. Journal of Thrombosis and Haemostasis. 104 (4), 811-822.
Ferland, G. (2012). Vitamin K and the nervous system: An overview of its actions. Advances in Nutrition. 3 (2), 204–212.
Iwamoto, J., Takeda, T., Sato, Y. (2004). Effects of vitamin K2 on osteoporosis. Current Pharmaceutical Design. 10 (21), 2557–2576.
Li, Y., Chen, J. et al. (2017). Effect of vitamin K2 on type 2 diabetes mellitus. Diabetes Research and Clinical Practice. 17 (3), 68-75.
Otten, H.J., Meyers, L.D., Eds, S. (2008). Government Food and Nutrition Information. The Dietary Reference Intakes: The Essential Guide to Nutrient Requirements. National Academies Press.
P. Szulc, P., Chapuy, M.C., Meunier, P.J. et al. (1996). Serum undercarboxylated osteocalcin is a marker of the risk of hip fracture: a three year follow-up study. Bone. 18 (5), 487-488.
Schwalfenberg, G.K. (2017). Vitamins K1 and K2: The Emerging Group of Vitamins Required for Human Health. Journal of Nutrition and Metabolism. 17 (6), 22-35.
Theuwissen, E. et al. (2012). Low-dose menaquinone-7 supplementation improved extra hepatic vitamin K status, but had no effect on thrombin generation in healthy subjects. British Journal of Nutrition. 108 (9), 1652-1657.
Yamaguchi, M. (2006). Regulatory mechanism of food factors in bone metabolism and prevention of osteoporosis. Yakugaku Zasshi. 126 (11), 1117–1137.
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