Vitamin K

In 1929 it was isolated from alfalfa. In 1943, Henrik Dam, for the discovery, and Edward Adelbert Doisy were awarded the joint Nobel Prize in Medicine for uncovering the chemical nature of vitamin K. Vitamin K1 is the trivial name for 2-methyl-3-phytyl-1,4-naphtoquinone (also α-phylloquinone). In addition, there is also vitamin K2 (2-methyl -3- difarnesyl -1,4- naphtoquinone), which is also known as menaquinone or also as farnoquinone. Vitamin K1 is found naturally in plant foods such as green leafy vegetables, while vitamin K2 is found primarily in animal foods and fermented foods (2).Vitamin K2 can be further subdivided into 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-naphtoquinone) menadione. Other vitamin K derivatives exist, but they are less important. The name phylloquinone originates from the word phyllos, which means leaf. The letter K was used after the Danish researcher Carl Peter Henrik Dam isolated from dried alfalfa leaves a fat-soluble substance that showed a balancing effect on blood clotting (coagulation vitamin) and for simplicity it was then called vitamin K.

Description

Vitamin K belongs to the fat-soluble vitamins and to the group of phylloquinones. Phylloquinones are a group of several substances: phylloquinone (vitamin K1), and menaquinone (vitamin K2), occur naturally, while 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, and vitamin K2 (menaquinone) is synthesized by bacteria. About half of the requirement of vitamin K2 is synthesized by intestinal bacteria. Vitamin K can be absorbed only 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. Furthermore, vitamin K is directly involved in bone formation via endogenous 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 to oxygen O. When exposed to light, vitamin K becomes inactive and rapidly loses its bioavailability. All substances with phylloquinone activity (K vitamins) are derived from the naturally non-occurring 2-methyl-1,4-naphthoquinone (menadione). Prerequisites for vitamin K activity include a lipophilic side chain (in trans configuration) in addition to the unsubstituted aromatic ring. Natural terpene chains with 20 carbon atoms are optimal. Side chains below 8 carbon atoms lead to inactivity except for menadione. Up to 100 compounds with vitamin K activity are known, but only three of them 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 (clotting). Vitamin K also plays a major role in the biosynthesis of proteins in bone, kidney, plasma and connective tissue. One of the most important functions of vitamin K is to regulate calcium retention. In other words, it promotes calcium storage in bone and prevents unwanted calcium storage in blood vessels and kidneys (3, 4). Some scientists believe that the roles of vitamin K1 and K2 are quite different, and many of them believe that these two subtypes should be classified as separate nutrients.

This is supported by a study conducted with 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 merit 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 resorption rate is 60-80 percent. Vitamin K2, on the other hand, enters the intestinal tissue by diffusion. Vitamins K1 and K2 pass through the blood to the bone marrow, liver and kidney. Here they can be stored for up to 14 days. The vitamins are excreted via the bile and partially 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 posttranslational introduction of a carboxyl group into the γ-position of the glutamine of specific proteins, changing their properties. Its most important function is its participation in the synthesis of various blood clotting factors.

Occurrence and supply

Numerous widely consumed foods are rich sources of vitamin K1, whereas K2 is less prevalent in our diet. The body can convert some vitamin K1 to vitamin K2, which is useful because the average amount of vitamin K1 consumed in the diet is about ten times the amount of vitamin K2 consumed in the diet. However, recent 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 intestinal bacteria in the colon. Some studies suggest that a broad-spectrum antibiotic may contribute to vitamin K2 deficiency (28, 29). The average level of vitamin K2 in the modern diet is surprisingly low. This vitamin is found mainly in certain animal and fermented foods that are not in the diet of most people. Rich animal sources of vitamin K2 include high-fat dairy products from grass-fed cows, egg yolks, and liver and other offal (39). Because 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, taking vitamin K2 supplements is a viable option. The benefits of vitamin K2 supplementation 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 cottage cheese
• 400 g mushrooms
• 500 g strawberries

Furthermore, the following foods, for example, 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 do the scientific studies say about this?

Vitamin K could help prevent heart disease

Calcium accumulation in the arteries around the heart is an important risk factor for heart disease (7, 8, 9). For this reason, anything that can prevent these calcium buildups may help prevent heart disease. It is believed that vitamin K can 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 atherosclerosis and this group also had a 57% lower risk of dying from heart disease (11).

Another study conducted with 16,057 women found that subjects with the highest vitamon 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 studies, which cannot prove the relationship between cause and effect. The few controlled studies that have been conducted used vitamin K1, which appears to be ineffective for this application. Therefore, more controlled studies are needed to further investigate the relationship between vitamin K2 intake and heart disease risk. However, there is a very plausible biological mechanism for the effectiveness of vitamin K2 and strong positive correlations regarding heart health in observational studies.

Abstract: 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 can 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 has already been 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 stable bone (14, 15). Interestingly, there is also substantial evidence from controlled studies showing that K2 may confer major benefits for bone health. A 3-year study of 244 postmenopausal women found that those taking vitamin K2 supplements had a much slower age-related reduction in bone mineral density (16).

Long-term studies conducted in Japan with women observed similar effects, although these studies used very high dosages. Of 13 studies, only one failed to find significant improvements. Seven of these studies that included fractures found that vitamin K2 reduced the risk of spinal fractures by 60%, the risk of hip fractures by 77%, and the risk of all non-spinal fractures by 81% (17). Consistent with these studies, vitamin K supplements are officially recommended in Japan for the prevention and treatment of osteoporosis (18). However, some researchers are not convinced, considering two large review studies 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, there have not yet been any human studies that have directly investigated this. However, based on studies conducted with animals 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 critical to bone metabolism that is activated via 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, working synergistically with vitamin K1 (24).

Abstract: Vitamin K2 is believed to play a critical role in dental health, although human studies on this 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 now 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 specific cancer types. Two clinical trials suggest that vitamin K2 may reduce the recurrence of liver cancer and prolong survival (25, 26). In addition to this, an observational study of 11,000 men found that higher vitamin K2 intake was associated with a 63% lower risk of advanced prostate cancer, whereas vitamin K1 had no effect (27). However, further high-quality studies are needed to draw firm conclusions.

Abstract: According to studies, 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, since up to 50% of the requirement can be formed in the intestine. Liver and chronic gastrointestinal diseases (diarrhea) promote vitamin K deficiency. However, the oral intake of antibiotics (growth inhibition of the vitamin K-providing intestinal bacteria) can lead to inhibition of the body's own hematopoiesis; however, this only occurs in the case of simultaneous malnutrition. Furthermore, vitamin K deficiency also frequently occurs in osteoporosis, where an increased loss of calcium is typical. As with other fat-soluble vitamins, deficiency symptoms can occur in the case of an intestinal fat resorption disorder (for example, in the case of bile duct obstruction). However, if vitamin K deficiency occurs, there is a prolongation of blood clotting. In infants, cerebral hemorrhages may occur. 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 overdose (hypervitaminosis)

Since vitamin K has no toxic effects (no toxic effects are known for 500 times the recommended amount), overdoses hardly ever occur. After injection of vitamin K in very high doses, allergic reactions and changes in blood composition may occur.

Antagonists

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

Demand

Determining vitamin K requirements is difficult due to analytical problems in determining this vitamin in foods and uncertainty about the level of synthesis by bacteria in the gut. There is a difference of opinion regarding the daily requirement of vitamin K. The German Society for Nutrition recommends: 65 µg for women and 80 µg for men per day. Since infants often suffer from vitamin K deficiency because breast milk has only a low vitamin K content, vitamin K prophylaxis is often recommended.

Demand in sport

70-140mg a day.

Conclusion

Vitamin K represents 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 point out that more 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 body's function. To maintain good health, you should therefore make sure to consume adequate amounts of vitamin K1 and K2 through 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