Vitamin K

It was isolated from alfalfa in 1929. In 1943, Henrik Dam, for the discovery, and Edward Adelbert Doisy received the joint Nobel Prize in Medicine for discovering the chemical nature of vitamin K. Vitamin K1 is the trivial name for 2-methyl-3-phytyl-1,4-naphthoquinone (also α-phylloquinone). There is also vitamin K2 (2-methyl -3- difarnesyl -1,4-naphthoquinone), which is also known as menaquinone or farnoquinone. Vitamin K1 is found naturally in plant foods such as green leafy vegetables, while vitamin K2 is primarily found in animal foods and fermented foods (2).Vitamin K2 can be divided into further subtypes, of which MK-4 and MK-7 are the most important.

Vitamin K3 is the name given to the exclusively artificially produced (2-methyl-1,4-naphthoquinone) menadione. There are other vitamin K derivatives, but these are less important. The name phylloquinone comes from the word phyllos, meaning leaf. The letter K was used after the Danish researcher Carl Peter Henrik Dam isolated a fat-soluble substance from dried alfalfa leaves, which showed a balancing effect on blood clotting (coagulation vitamin) and was then called vitamin K for the sake of simplicity.

Description

Vitamin K is a fat-soluble vitamin and belongs to the group of phylloquinones. Phylloquinones are a group of several substances: phylloquinone (vitamin K1) and menaquinone (vitamin K2) occur naturally, whereas menadione (vitamin K3), hydroxyquinone (vitamin K4) and others are synthetic products that are no longer commercially available today (2005). Vitamin K1 (phylloquinone) is synthesized by plants, vitamin K2 (menaquinone) by bacteria. About half of the vitamin K2 requirement is synthesized by intestinal bacteria. Vitamin K can only be absorbed with the help of bile acid. An increase in absorption is enhanced by the simultaneous intake of fats. Vitamin K is involved in the production of various blood clotting factors in the liver. Vitamin K is also directly involved in bone formation via the body's own proteins, for example osteocalcin, and via functions within the metabolism of calcium.

Due to the heat stability of the vitamin K group, little vitamin loss occurs during preparation, especially during cooking. Vitamin K is also stable towards oxygen O. When exposed to light, vitamin K becomes inactive and quickly loses its bioavailability. All substances with phylloquinone activity (K vitamins) are derived from 2-methyl-1,4-naphthoquinone (menadione), which does not occur naturally. In addition to the unsubstituted, aromatic ring, a lipophilic side chain (in trans configuration) is a prerequisite for vitamin K activity. Natural terpene chains with 20 carbon atoms are optimal. Side chains with less than 8 carbon atoms lead to inactivity, except in the case of menadione. Up to 100 compounds with vitamin K activity are known, of which only three are of importance.

Task/function

The main function of vitamin K is that it is necessary for the synthesis of certain proteins (prothrombin), which play an important role in blood clotting. These factors are used to stop bleeding (coagulation). Vitamin K also plays a major role in the biosynthesis of proteins in the bones, kidneys, plasma and connective tissue. One of the most important functions of vitamin K is to regulate calcium deposits. In other words, it promotes calcium deposition in the bones and prevents unwanted calcium deposition in the blood vessels and kidneys (3, 4). Some scientists believe that the roles of vitamin K1 and K2 are quite distinct and many of them believe that these two subtypes should be classified as separate nutrients.

This is supported by a study conducted in animals which showed that vitamin K2 (MK-4) prevented calcification of blood vessels, while vitamin K1 was unable to do so (5). Controlled human studies generally observe that vitamin K2 supplements improve bone and heart health, while vitamin K1 does not appear to have any benefits in this regard (6). However, further human studies are needed to fully understand the functional differences between vitamin K1 and K2.

As a fat-soluble vitamin, vitamin K1 is bound to the absorption of fats. The absorption rate is 60-80 percent. Vitamin K2, on the other hand, enters the intestinal tissue by diffusion. Vitamins K1 and K2 reach the bone marrow, liver and kidneys via the blood. They can be stored here for up to 14 days. The vitamins are excreted via the bile and partly via the kidneys. The biological activity of vitamin K is due to its ability to switch between its oxidized (quinone) and reduced (hydroquinone) forms. The essential importance of vitamin K lies in its contribution to the post-translational introduction of a carboxyl group into the γ-position of the glutamine of specific proteins, thereby changing their properties. Its most important function is its involvement in the synthesis of various blood coagulation factors.

Occurrence and intake

Many common foods are rich sources of vitamin K1, whereas K2 is less common in our diet. The body can convert some vitamin K1 into vitamin K2, which is useful as the average amount of vitamin K1 taken in with food is about ten times the amount of vitamin K2 taken in with food. However, current research suggests that this conversion process is inefficient. For this reason, you will benefit more from a higher direct intake of vitamin K2.

Vitamin K2 is also produced by gut bacteria in the large intestine. Some research suggests that broad-spectrum antibiotics may contribute to vitamin K2 deficiency (28, 29). The average level of vitamin K2 in the modern diet is surprisingly low. This vitamin is mainly found in certain animal and fermented foods that are not part of most people's diets. Rich animal sources of vitamin K2 include high-fat dairy products from grass-fed cows, egg yolks, and liver and other offal (39). Since vitamin K is fat-soluble, this means that low-fat animal products do not contain much vitamin K.

Animal foods contain the MK-4 subtype of vitamin K2, while fermented foods such as sauerkraut and miso contain more of the longer subtypes from MK-5 to MK-14 (31). If you don't have access to these foods, or don't like them, then taking vitamin K2 supplements is a viable option. The benefits of supplementing with vitamin K2 can be further enhanced when vitamin K2 is combined with a vitamin D supplement, as these two vitamins have synergistic effects.

Here is a brief overview of the vitamin K content of some foods:

The daily dose of 65 µg (1 µg, also 1 mcg = millionth = 0.000 001 g = 0.001 mg) of vitamin K1 is contained, for example, in:

• 15 g chives
• 25 g Brussels sprouts
• 50 g calf's liver
• 3 eggs
• 220 g quark
• 400 g mushrooms
• 500 g strawberries

The following foods also contain vitamin K1 (1 mg = thousandth = 0.001 g):

• 200 g Brussels sprouts 1.14 mg
• 300 g wholemeal bread 37 mcg (0.037 mg)
• 200 g cauliflower 0.60 mg
• 30 g muesli 15 mcg
• 200 g kohlrabi 1.00 mg

What other health benefits does vitamin K have and what does the scientific evidence say about this?

Vitamin K could help prevent heart disease

Calcium build-up in the arteries around the heart is a major risk factor for heart disease (7, 8, 9). For this reason, anything that can prevent this calcium build-up can help prevent heart disease. Vitamin K is believed to help prevent calcium from being deposited in the arteries (10). In a study lasting 7 to 10 years, subjects with the highest vitamin K2 intake were 52% less likely to develop hardening of the arteries and 57% less likely to die from heart disease (11).

Another study of 16,057 women found that subjects with the highest vitamin K2 intake had a significantly lower risk of heart disease - for every 10 mcg of vitamin K2 these women consumed, their risk of heart disease decreased by 9% (12). Vitamin K1 had no effect in any of these studies. However, it should be kept in mind that the above studies are observational and cannot prove a cause and effect relationship. The few controlled studies that have been conducted used vitamin K1, which appears to be ineffective for this application. Further controlled studies are therefore needed to investigate the relationship between vitamin K2 intake and the risk of heart disease in more detail. However, there is a very plausible biological mechanism for the effectiveness of vitamin K2 and strong positive correlations with heart health in observational studies.

Summary: A higher intake of vitamin K2 is associated with a reduced risk of heart disease. Vitamin K1, on the other hand, appears to be ineffective in this regard.

Vitamin K may help improve bone health and reduce the risk of osteoporosis

Osteoporosis, which literally means "porous bones", is a widespread problem in the Western world. This condition particularly affects older women and rapidly increases the risk of fractures. As already mentioned, vitamin K2 plays a central role in calcium metabolism - and most calcium is found in the bones. Vitamin K2 activates the calcium-binding actions of two proteins - matrix GLA protein and osteocalcin - which help build and maintain strong bones (14, 15). Interestingly, there is also substantial evidence from controlled studies showing that K2 may have major benefits for bone health. A 3-year study of 244 postmenopausal women found that the women who took vitamin K2 supplements had a much slower age-related reduction in bone mineral density (16).

Long-term studies of women in Japan have shown similar effects, although these studies used very high doses. Of 13 studies, only one failed to show significant improvements. Seven of these studies, which included fractures, found that vitamin K2 reduced the risk of spine fractures by 60%, hip fractures by 77% and all non-spine fractures by 81% (17). In line with these studies, vitamin K supplements are officially recommended in Japan for the prevention and treatment of osteoporosis (18). However, some scientists are not convinced, as they consider two large review studies to be insufficient as a basis for recommending the use of vitamin K supplements for this purpose (19, 20).

Summary: Vitamin K2 plays an essential role in bone metabolism and studies suggest that it may help prevent osteoporosis and fractures.

Vitamin K could improve dental health

Scientists have speculated that vitamin K2 may have effects on dental health. However, no human studies have yet directly investigated this. However, based on animal studies and the role that vitamin K plays in bone metabolism, it is realistic to assume that this nutrient has an impact on dental health. One of the primary regulatory proteins in dental health is osteocalcin - the same protein that is critical for bone metabolism and is activated by vitamin K2 (21). Osteocalcin triggers a mechanism that stimulates the growth of new dentin. Dentin is the calcified tissue beneath tooth enamel (22, 23). Vitamin A and vitamin D are also believed to play an important role here and work synergistically with vitamin K1 (24).

Summary: Vitamin K2 is believed to play a crucial role in dental health, although human studies are still lacking.

Vitamin K could help fight cancer

Cancer is a common cause of death in the western world. Even though modern medicine has found many ways to cure cancer, new cases of cancer continue to occur. For this reason, effective prevention strategies are of paramount importance. Interestingly, several studies have been conducted on vitamin K2 and certain types of cancer. Two clinical studies suggest that vitamin K2 can reduce the recurrence of liver cancer and prolong survival (25, 26). In addition, an observational study of 11,000 men found that higher vitamin K2 intake was associated with a 63% lower risk of advanced prostate cancer, while vitamin K1 had no effect (27). However, further high-quality studies are needed to draw firm conclusions.

Summary: Studies suggest that vitamin K2 may improve survival rate and duration in patients with liver cancer. Men who consume the highest amounts of vitamin K2 also appear to have a lower risk of advanced liver cancer.

Deficiency symptoms (hypovitaminosis)

Vitamin K deficiency is rather rare, as up to 50% of the requirement can be produced in the intestine. Liver and chronic stomach and intestinal diseases (diarrhea) promote a vitamin K deficiency. The oral intake of antibiotics (growth inhibition of the intestinal bacteria that supply vitamin K) can, however, lead to the inhibition of the body's own blood formation; this only occurs, however, in the case of simultaneous malnutrition. Furthermore, osteoporosis, where an increased loss of calcium is typical, often leads to a vitamin K deficiency. As with other fat-soluble vitamins, an intestinal fat absorption disorder (e.g. bile duct obstruction) can lead to deficiency symptoms. However, if there is a vitamin K deficiency, blood clotting is prolonged. Cerebral hemorrhages can occur in infants. Digestive disorders, chronic liver disease and bleeding in various tissues and organs, such as the nasal mucosa, gastrointestinal tract and muscles, are possible.

Consequences of an overdose (hypervitaminosis)

As vitamin K has no toxic effect (no toxic effects are known for 500 times the recommended amount), overdoses rarely occur. After injecting very high doses of vitamin K, allergic reactions and changes in the blood composition can occur.

Antagonists

It is known that vitamin K is essential for the synthesis of coagulation factors (prothrombin). The presence of vitamin K antagonists (e.g. warfarin, dicumarol) clarified the mode of action of this vitamin for the first time. Dicumarol present in spoiled clover, for example, led to life-threatening bleeding in cattle. Warfarin is also used as a rat poison. Cows fed with dicumarol have an abnormal prothrombin which, unlike the normal prothrombin, no longer binds Ca2+. This is due to a change in an amino acid in the prothrombin. Phenprocoumon is often used as an antagonist to inhibit blood clotting.

Need

Determining the vitamin K requirement is difficult due to analytical problems in determining this vitamin in food and the uncertainty about the level of synthesis by bacteria in the intestine. There are different assessments regarding the daily requirement of vitamin K. The German Nutrition Society recommends: 65 µg for women and 80 µg for men per day. As infants often suffer from a vitamin K deficiency due to the low vitamin K content of breast milk, vitamin K prophylaxis is often recommended.

Requirements in sport

70-140mg per day.

Conclusion

Vitamin K is a group of nutrients that can be divided into vitamins K1 and K2. Vitamin K1 is involved in blood clotting and vitamin K2 promotes bone and cardiovascular health. However, more studies are needed to investigate the different roles of these two subtypes of vitamin K. Some scientists are convinced that people with heart disease should take vitamin K2 supplements regularly, while others suggest that further studies are needed before solid recommendations can be made. All in all, however, it is clear that vitamin K plays an essential role in the functioning of the body. To maintain good health, you should therefore make sure to consume adequate amounts of vitamin K1 and K2 in your diet.

References

1. https://link.springer.com/chapter/10.1007/978-1-4899-1789-8_19
2. https://www.ncbi.nlm.nih.gov/pubmed/17158229
3. https://www.ncbi.nlm.nih.gov/pubmed/3530901
4. https://www.ncbi.nlm.nih.gov/pubmed/22516724
5. https://www.ncbi.nlm.nih.gov/pubmed/14654717
6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5494092/
7. https://www.ncbi.nlm.nih.gov/pubmed/23529983
8. https://www.ncbi.nlm.nih.gov/pubmed/18367736
9. https://www.ncbi.nlm.nih.gov/pubmed/14976978
10. https://www.ncbi.nlm.nih.gov/pubmed/22516724
11. https://www.ncbi.nlm.nih.gov/pubmed/15514282
12. https://www.ncbi.nlm.nih.gov/pubmed/1917905
13. https://www.ncbi.nlm.nih.gov/pubmed/22516723
14. https://www.ncbi.nlm.nih.gov/pubmed/22516726
15. https://www.ncbi.nlm.nih.gov/pubmed/23410565
16. https://link.springer.com/article/10.1007%2Fs00198-013-2325-6
17. https://www.ncbi.nlm.nih.gov/pubmed/16801507
18. https://www.ncbi.nlm.nih.gov/pubmed/18830045
19. http://onlinelibrary.wiley.com/doi/10.1002/mnfr.201300950/full
20. https://link.springer.com/article/10.1007%2Fs00774-011-0287-3
21. https://www.ncbi.nlm.nih.gov/pubmed/9076586
22. https://www.ncbi.nlm.nih.gov/pubmed/16295569
23. https://www.ncbi.nlm.nih.gov/pubmed/17055908
24. https://www.ncbi.nlm.nih.gov/pubmed/8466530
25. https://www.ncbi.nlm.nih.gov/pubmed/16400650
26. https://www.ncbi.nlm.nih.gov/pubmed/23225445
27. https://www.ncbi.nlm.nih.gov/pubmed/18400723
28. https://www.ncbi.nlm.nih.gov/pubmed/1492156
29. https://www.ncbi.nlm.nih.gov/pubmed/7895417
30. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3321250/
31. https://www.ncbi.nlm.nih.gov/pubmed/11356998
32. https://www.ncbi.nlm.nih.gov/pubmed/21155624