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Vitamin K2 MK-7 (Menaquinone-7)

Vitamin K was first identified in 1929 as a nutrient essential for blood clotting, a process known scientifically as coagulation (haemostasis). The discovery of this nutrient was published in a German scientific journal, where it was referred to as "Koagulationsvitamin," which is where the "K" in vitamin K comes from. While often associated with its role in blood clotting, Vitamin K actually refers to a group of fat soluble vitamins that have similar chemical structures and offer a range of health benefits. There are various types of Vitamin K, but the two most commonly found in the human diet are:

  • Vitamin K1 (phytomenadione/phylloquinone): primarily found in plant foods like leafy green vegetables.

  • Vitamin K2 (menaquinone): primarily of bacterial origin and found in animal foods and fermented foods.

Vitamin K2 is a form of vitamin K that can be divided into several different subtypes with longer side chains from MK-5 through MK-15, including MK-4 and MK-7. Menaquinone-7, also known as vitamin K2 MK-7, is produced by intestinal microbiota (bacteria) and conversion of K1 to K2 by beneficial bacteria in the human intestine, and can be found in fermented foods such as natto and cheese. This nutrient is rare in the Western diet, but has been shown to have a significant impact on various aspects of overall health. Some experts believe it may be the missing link between diet and chronic health conditions. There is ongoing debate among scientists regarding the distinct roles of vitamins K1 and K2 in the body. One key difference between these two forms of vitamin K is their half-life, with vitamin K2 (menaquinone-7) having a longer half-life than vitamin K1 (phytomenadione).

Thought to be associated with its longer side chain, the longer half-life allows vitamin K2 to circulate in the blood for longer periods of time and be absorbed by tissues throughout the body, with measurable levels detected up to 72 hours after ingestion. In contrast, vitamin K1 is primarily transported to the liver and cleared within 8 hours. Another important difference between these two forms is that vitamin K2 supplements, specifically the MK-7 form, have been shown to have beneficial effects on bone and heart health, while vitamin K1 appears to have a more specific role in the essential process of blood clotting (coagulation or haemostasis). These differences are important for understanding the distinct roles that vitamins K1 and K2 play in the body.

Natural dietary sources of menaquinone-7 (K2 MK-7)

Vitamin K2, particularly the form called menaquinone-7 (MK-7), is a type of vitamin K only found in certain foods. Natural sources of vitamin K2 MK-7 are not commonly consumed in the modern diet, leading to low intake of this important nutrient. All others forms of vitamin K are absorbed in the small intestine through a process requiring bile salts, while most of the menaquinone (vitamin K2) is produced in the colon where bile salts are lacking. While previous research suggested that bacterial synthesis of vitamin K may be significant, current evidence suggests that the contribution of this process to vitamin K status is much smaller, although the exact amount remains uncertain.

Here are the more potent natural dietary sources of menaquinone-7 (vitamin K2 MK-7):

  • Natto: Natto is a traditional Japanese dish made from fermented soybeans, and it is a rich source of vitamin K2 MK-7. A serving of natto provides about 1000 micrograms (mcg) of vitamin K2 MK-7.

  • Chicken liver: Chicken liver is a good source of vitamin K2 MK-7, with a 100-gram serving providing about 90 mcg of vitamin K2 MK-7.

  • Egg yolks: Egg yolks are a good source of vitamin K2 MK-7, with a single yolk providing about 15 mcg of vitamin K2 MK-7. Eggs are also a good source of vitamin K2 MK-4.

  • Cheese: Some types of cheese, such as Gouda, Brie, and Edam, are good sources of vitamin K2 MK-7. A 1-ounce serving of Gouda cheese provides about 15 mcg of vitamin K2 MK-7.

  • Butter: Butter is a good source of vitamin K2 MK-7, with a tablespoon providing about 10 mcg of vitamin K2 MK-7. Butter is also a good source of vitamin K2 MK-4.

  • Chicken: Chicken is a good source of vitamin K2 MK-7, with a 100-gram serving providing about 12 mcg of vitamin K2 MK-7. Chicken is also a good source of vitamin K2 MK-4.

It is worth noting that the amount of vitamin K2 you can obtain from food varies based on factors such as the soil in which it was grown, the processing methods used, the form in which it is present, and the presence of other substances that may interfere its absorption.

While dietary intake of vitamin K2 is important for maintaining adequate levels in the body, it is possible to obtain this nutrient in the bioavailable form of K2 MK-7 with vitamin supplements. However, the best way to get the essential nutrients your body needs is to eat a variety of whole, unprocessed, fruits, vegetables, nuts, seeds, and other plant-based foods. These types of food ensure that you are getting a wide range of nutrients, which may include vitamin K2, and should not be replaced by vitamin and mineral supplements alone.

Protective effect of menaquinone-7 against cardiovascular disease

Vitamin K is a fat-soluble nutrient that plays a vital role in the activation of Gla-proteins, which are proteins that contain a specific type of amino acid called gamma-carboxyglutamic acid (Gla). Gla-proteins have a wide range of functions in the body, including regulating blood clotting and calcium metabolism. To date, 15 Gla-proteins have been identified in humans, but it is believed that there may be up to 100 yet to be discovered. The activation of Gla-proteins requires the presence of vitamin K, which acts as a cofactor in the carboxylation process, adding a carboxyl group to the Gla residues on the protein. This process, known as carboxylation, activates the Gla-proteins and enables them to perform their various functions.

Insufficient levels of vitamin K can lead to an excess of inactive osteocalcin in the bloodstream. Osteocalcin is a Gla-protein that is involved in bone metabolism and helps to regulate the uptake and distribution of calcium in the body. When levels of vitamin K are insufficient, osteocalcin remains uncarboxylated and is unable to perform its functions properly. This can result in calcium not being properly delivered to the bones, leading to porous bones, and being deposited in the arteries, contributing to arterial calcification. Arterial calcification is a significant risk factor for heart disease and can lead to the hardening and narrowing of the arteries, which can impede blood flow and increase the risk of heart attacks and strokes.

Vitamin K is thought to help prevent calcium from accumulating in the arteries and may reduce the risk of heart disease. Cardiovascular disease is often thought of as being caused by high cholesterol levels, which can lead to the formation of plaques on the inner walls of the arteries (atherosclerosis). However, it is also important to note that arteriosclerosis, which is the hardening of the arteries due to calcium deposits in their muscular walls, can also be a major cause of sudden death in young men whose cholesterol levels are normal.. One of the vitamin K2-dependent proteins, matrix Gla-protein (MGP), is a potent inhibitor of tissue calcification and is produced by small muscle cells in the blood vessels. When activated by vitamin K2, MGP binds to and inhibits the protein bone morphological protein-2 (BMP-2), which promotes calcium deposition in blood vessels. Vitamin K2 also helps to maintain the elasticity of blood vessels by protecting elastin, a protein that is essential for arterial wall elasticity. Elastin can be damaged and new production can be hindered by calcium deposits. Adequate intake of vitamin K2 has been linked to a lower risk of arterial calcification and coronary artery disease, and some studies suggest that vitamin K2 supplementation may also reduce the risk of stroke.

Benefits of menaquinone-7 for osteoporosis

For nearly four decades, research has shown a connection between osteoporotic fractures and vitamin K deficiency. Osteoporosis, a condition characterised by weak and porous bones, is a common issue in Western countries and poses a significant risk of fractures, especially in older women. Vitamin K, including both vitamin K1 and K2, plays a crucial role in bone metabolism by activating proteins involved in bone mineralisation. Specifically, vitamin K2 activates the calcium binding actions of two proteins mentioned above - matrix GLA protein and osteocalcin, the latter of which helps to build and maintain strong bones. In addition, vitamin K2 works synergistically with vitamin D3 to increase the production of Gla-proteins, such as osteocalcin, in osteoblasts (cells responsible for building bones) while also inhibiting the production of osteoclasts (cells that break down bone). These actions help to support healthy bone development and maintenance.

Several observational studies, such as the Rotterdam Study and the Prospective Urban Rural Epidemiology (PURE) study, have found that higher intake of dietary vitamin K2 is associated with increased bone density and a lower risk of fractures in both men and women. Based on a substantial body of clinical evidence, Japanese guidelines now officially recommend the use of vitamin K supplements for the prevention and treatment of osteoporosis.

Potential for menaquinone-7 in cancer prevention

In Western countries, cancer is a leading cause of death, despite advances in medical treatments. In order to combat this issue, it is essential to find effective prevention methods. One avenue of research that has garnered attention is the potential link between vitamin K2 and certain types of cancer. Some observational studies, such as the Japan Public Health Center-Based Prospective Study and the European Prospective Investigation into Cancer and Nutrition (EPIC)-Heidelberg study, have found that higher intake of dietary vitamin K2 is associated with a lower risk of certain types of cancer, such as liver and prostate cancer, and increased survival times. 

What are the symptoms of vitamin K2 deficiency?

Vitamin K2 is an essential nutrient that plays a vital role in bone health and cardiovascular function. A deficiency in vitamin K2 is relatively rare and may not cause any noticeable symptoms. However, a deficiency in vitamin K2 may lead to an increased risk of osteoporosis (a condition characterised by weak and brittle bones) and cardiovascular disease.

Adults at risk for vitamin K deficiency include those taking vitamin K antagonists and individuals with significant liver damage or disease. Some research suggests that vitamin K2 deficiency may be more common in people with certain medical conditions, such as Crohn's disease or celiac disease, which can affect the absorption of nutrients from the diet. In these cases, a deficiency in vitamin K2 may contribute to the development of osteoporosis or cardiovascular disease.

If you are concerned about a deficiency in vitamin K2, it is important to speak with a health professional. They can help diagnose the cause of your symptoms and recommend appropriate treatment.

What are the potential side effects of taking vitamin K2 MK-7 supplements?

Vitamin K2 MK-7 supplements are generally well tolerated and have a low risk of side effects when taken in recommended amounts. However, taking excessive amounts of vitamin K2 MK-7 can cause side effects, including:

  • Nausea: Consuming large amounts of vitamin K2 MK-7 may cause nausea.

  • Diarrhea: Vitamin K2 MK-7 supplements may cause diarrhea in some people.

  • Headache: Some people may experience headaches after taking high doses of vitamin K2 MK-7.

  • Rash: Taking high doses of vitamin K2 MK-7 may cause a rash to develop on the skin.

  • Fatigue: Large amounts of vitamin K2 MK-7 may cause weakness and fatigue.

It is important to note that these side effects are typically associated with taking large amounts of vitamin K2 MK-7, well above the recommended daily intake. It is important to speak with a health professional before taking vitamin K2 MK-7 supplements to ensure that you are taking the appropriate amount.

Vitamin K2 MK-7 supplements are generally safe when taken in recommended amounts. However, as with any supplement, it is important to speak with a health professional before starting to ensure that they are safe and appropriate for you.

Can vitamin K2 MK-7 supplements interact with other medications or supplements?

Yes, vitamin K2 MK-7 supplements can interact with certain medications and supplements. Some medications and supplements that may interact with vitamin K2 MK-7 include:

  • Warfarin (Coumadin), may interfere with their effectiveness.

  • Antibiotics: Some antibiotics, such as ciprofloxacin and norfloxacin, may interfere with the absorption of vitamin K2 MK-7.

  • Other supplements: Some supplements, such as large doses of vitamin E, may interact with vitamin K2 MK-7. It is important to speak with a healthcare professional about potential interactions between vitamin K2 MK-7 and any other supplements you are taking.

It is important to speak with a health professional before taking vitamin K2 MK-7 supplements to ensure that they are safe and appropriate for you. They can help you understand any potential interactions with other medications or supplements you are taking.

Is it safe to take vitamin K2 MK-7 supplements if I have a particular health condition?

Vitamin K2 MK-7 supplements are generally safe and well tolerated when taken in recommended amounts. However, if you have a particular health condition, it is important to speak with a health professional before taking vitamin K2 MK-7 supplements to ensure that they are safe and appropriate for you. Some conditions that may be affected by vitamin K2 MK-7 supplements include:

  • Bleeding disorders: Vitamin K2 MK-7 is necessary for blood clotting, so taking it may interfere with the effectiveness of blood thinners if you have a bleeding disorder.

  • Antibiotic use: Some antibiotics may interfere with the absorption of vitamin K2 MK-7. It is important to speak with a health professional about the appropriate amount of vitamin K2 MK-7 to take if you are taking antibiotics.

  • Other medications: Vitamin K2 MK-7 supplements may interact with certain medications, such as blood thinners. It is important to speak with a health professional about potential interactions between vitamin K2 MK-7 and any medications you are taking.

It is always important to speak with a health professional before starting any new supplement to ensure that it is safe and appropriate for you. They can help you understand any potential risks or interactions with your specific health condition and any medications or supplements you are taking.

Conclusion

In conclusion, menaquinone-7, or vitamin K2, is a form of vitamin K that is produced by bacteria in the human intestine and found in fermented foods. Adequate intake of vitamin K2 is necessary for normal blood coagulation and the prevention of bleeding disorders. It also has potential benefits in the prevention of osteoporosis, cardiovascular disease, and certain types of cancer. 

It is worth noting that vitamin K2 MK-7 supplements may interact with certain medications or supplements, and it may have side effects in some people. If you are currently taking any medications or supplements, or if you have any underlying medical conditions, you should speak to your health professional before taking vitamin K2 MK-7 or any other nutritional supplement. Your health professional can help you determine if vitamin K2 MK-7 is safe and appropriate for you, based on your individual circumstances and medical history.

References and additional reading

  • Beulens, J. W., Bots, M. L., Atsma, F., Bartelink, M. L., Prokop, M., Geleijnse, J. M., ... & Witteman, J. C. (2009). High dietary menaquinone intake is associated with reduced coronary calcification. Atherosclerosis, 203(2), 489-493. https://doi.org/10.1016/j.atherosclerosis.2008.07.010PMID: 18722618.

  • Webb, Garth. “Modern Nutrition in Health and Disease, 9th edition. M. E. Shils, J. A. Olsen, M. Shike and A. C. Ross (editors). 1999. Baltimore: Williams & Wilkins. ISBN 0-683-30769-X.” British Journal of Nutrition 82 (1999): 331 - 332. doi :10.1017/S0007114599001555.

  • Schurgers LJ, Teunissen KJ, Hamulyák K, Knapen MH, Vik H, Vermeer C. Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7. Blood. 2007 Apr 15;109(8):3279-83. doi: 10.1182/blood-2006-08-040709. Epub 2006 Dec 7. PMID: 17158229.

  • Gast GC, de Roos NM, Sluijs I, Bots ML, Beulens JW, Geleijnse JM, Witteman JC, Grobbee DE, Peeters PH, van der Schouw YT. A high menaquinone intake reduces the incidence of coronary heart disease. Nutr Metab Cardiovasc Dis. 2009 Sep;19(7):504-10. doi: 10.1016/j.numecd.2008.10.004. Epub 2009 Jan 28. PMID: 19179058.

  • Geleijnse JM, Vermeer C, Grobbee DE, Schurgers LJ, Knapen MH, van der Meer IM, Hofman A, Witteman JC. Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study. J Nutr. 2004 Nov;134(11):3100-5. doi: 10.1093/jn/134.11.3100. PMID: 15514282.

  • Haugsgjerd TR, Egeland GM, Nygård OK, Vinknes KJ, Sulo G, Lysne V, Igland J, Tell GS. Association of dietary vitamin K and risk of coronary heart disease in middle-age adults: the Hordaland Health Study Cohort. BMJ Open. 2020 May 21;10(5):e035953. doi: 10.1136/bmjopen-2019-035953. PMID: 32444431; PMCID: PMC7247390.

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  • Capozzi A, Scambia G, Migliaccio S, Lello S. Role of vitamin K2 in bone metabolism: a point of view and a short reappraisal of the literature. Gynecol Endocrinol. 2020 Apr;36(4):285-288. doi: 10.1080/09513590.2019.1689554. Epub 2019 Nov 12. PMID: 31711322.

  • Platonova K, Kitamura K, Watanabe Y, Takachi R, Saito T, Kabasawa K, Takahashi A, Kobayashi R, Oshiki R, Solovev A, Iki M, Tsugane S, Sasaki A, Yamazaki O, Watanabe K, Nakamura K. Dietary calcium and vitamin K are associated with osteoporotic fracture risk in middle-aged and elderly Japanese women, but not men: the Murakami Cohort Study. Br J Nutr. 2021 Feb 14;125(3):319-328. doi: 10.1017/S0007114520001567. Epub 2020 May 7. PMID: 32378495.

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  • Mandatori D, Pelusi L, Schiavone V, Pipino C, Di Pietro N, Pandolfi A. The Dual Role of Vitamin K2 in "Bone-Vascular Crosstalk": Opposite Effects on Bone Loss and Vascular Calcification. Nutrients. 2021 Apr 7;13(4):1222. doi: 10.3390/nu13041222. PMID: 33917175; PMCID: PMC8067793.

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  • Knapen, M.H.J., Schurgers, L.J. & Vermeer, C. Vitamin K2 supplementation improves hip bone geometry and bone strength indices in postmenopausal women. Osteoporos Int 18, 963–972 (2007). https://doi.org/10.1007/s00198-007-0337-9PMID: 17287908; PMCID: PMC1915640.

  • Knapen MH, Braam LA, Drummen NE, Bekers O, Hoeks AP, Vermeer C. Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women. A double-blind randomised clinical trial. Thromb Haemost. 2015 May;113(5):1135-44. doi: 10.1160/TH14-08-0675. Epub 2015 Feb 19. PMID: 25694037.

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  • Apalset EM, Gjesdal CG, Eide GE, Tell GS. Intake of vitamin K1 and K2 and risk of hip fractures: The Hordaland Health Study. Bone. 2011 Nov;49(5):990-5. doi: 10.1016/j.bone.2011.07.035. Epub 2011 Aug 2. PMID: 21839190.

  • Rizzoli, R., Biver, E, & Bonjour, J. P. (2012). Vitamin K and the prevention of fractures: systematic review and meta-analysis of randomized controlled trials. Osteoporosis International, 23(12), 2551-2561.

  • Schuurman, A. G., van den Brandt, P. A., Dorant, E., & Goldbohm, R. A. (1999). A prospective cohort study on vitamin K intake and hip fractures. The American Journal of Clinical Nutrition, 69(1), 74-79.

  • Gijsbers BL, Jie KS, Vermeer C. Effect of food composition on vitamin K absorption in human volunteers. Br J Nutr. 1996 Aug;76(2):223-9. doi: 10.1079/bjn19960027. PMID: 8813897.

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Other potential benefits of menaquinone-7

In addition to the health benefits mentioned above, there is some evidence to suggest that vitamin K2 may have other potential benefits.

Vitamin K2 has been shown to have a protective effect against oxidative stress and inflammation in the brain, which may be beneficial in the prevention and management of neurodegenerative diseases such as Alzheimer's disease (Suttie, 2006).

There is also evidence to suggest that vitamin K2 may have a protective effect against liver disease and liver cancer. Some studies have found that vitamin K2 may help to reduce the severity of liver fibrosis and improve liver function in individuals with liver disease (Wang et al., 2013).

Vitamin K2 has also been shown to have potential benefits in the management of diabetes. Some studies have found that vitamin K2 may improve insulin sensitivity and help to lower blood sugar levels in individuals with diabetes (Shea et al., 2012).

References

  • Suttie, J. W. (2006). The importance of menaquinones (vitamin K2) in human health. Annual Review of Nutrition, 26, 195-220.

  • Shea, M. K., O'Donnell, C. J., Hoffmann, U., Dallal, G., Dawson-Hughes, B., & Ordovas, J. M. (2012). Vitamin K supplementation and improvement in insulin resistance in older men and women. The American Journal of Clinical Nutrition, 96(6), 1326-1334.

  • Wang, Y., Zhang, Y., Lu, J., Chen, J., Liu, C., & Zhang, H. (2013). Vitamin K2 ameliorates liver fibrosis by inhibiting the activation of hepatic stellate cells and myofibroblasts. International Journal of Molecular Medicine, 31(6), 1423-1430.

 

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