# 7.4 Vitamin K

Vitamin K is a group of structurally similar, fat-soluble vitamins that the human body needs for posttranslational modification of certain proteins required for blood coagulation, and in metabolic pathways in bone and other tissue. Vitamin K, because it is fat soluble, is stored in the liver and the fat stores in the body. Vitamin K is called as such due to its German name, “Koagulationsvitamin.” It is sometimes referred to as the clotting vitamin because it activates blood clotting factors. Vitamin K is also involved in the mineralization of the bones. Vitamin K refers to a family of compounds , the most common consumed form being phylloquinone (vitamin K1) which is found in plants.

## 7.4.1 Sources

Vitamin K is found in a number of foods, including leafy greens, cauliflower and, if you consider it a food, liver. Vitamin K is available in three forms, K1 or phylloquinone, K2 or menaquionone, and K3 or menaphthone or menadione. As aforementioned, K1 is the most commonly consumed form of the vitamin. Phylloquinone can be found in plants- specifically green leafy vegetables. This includes but is not limited to broccoli, spinach, kale, Brussels sprouts and even cauliflower. K1 is also found in plant oils typically used for cooking, such as olive, canola, and soybean oils. Interestingly, phylloquinones have greater bioavailability in oil form than in raw plant form; this may, however, be slightly decreased during hydrogenation process. The amount of K1 available also depends on the amount of chlorophyll, green pigmentation produced by the plant- dark leafy green vegetables will have a greater abundance than lighter less leafy vegetables (Torbergsen et al., 2015). Contrastingly, Vitamin K2 is most commonly synthesized in the animal gastrointestinal tract as microbacteria. K2 is also commonly found in fermented foods. Foods rich in menaquinones include beef liver and cheese products. K2 is naturally produced in the large intestine and it is believed that this compromises approximately 50 percent of the necessary vitamin K requirement of humans (Shearer, Fu, & Booth, 2012). Because this constitutes a vast majority of our requirement, upon birth, newborns are typically given a Vitamin K shot. Newborns have a sterile gut and therefore no bacteria to synthesize vitamin K. The fetus obtains vitamin K from its mother by transplacental transfer.
There is little known about Vitamin K3 except that it is found already formed in food but not in substantial doses. However, the chief source of vitamin K is synthesis by bacteria in the large intestine, and in most cases, absence of dietary vitamin K is not at all deleterious. Vitamin K is a fat-soluble vitamin and both dietary and microbial vitamin K are absorbed into intestinal lymph along with other lipids.
Vitamin K is a vitamin that can be found in multiple food sources but is also produced in the body. The GI tract contains bacteria that can synthesize vitamin K in small amounts. The specific type of Vitamin K that is produced in the GI tract this way is called menaquinone, or Vitamin K2. The rest of the Vitamin K a person needs can be obtained from the diet. Examples of foods containing quality amount of Vitamin K are spinach, kale, collards, bib lettuce, sprouts, cabbage, and other leafy greens. Some fruits and vegetable oils also have Vitamin K sources. Fruits that are a good source of Vitamin K are avocado and kiwi and a good oil source is either soybean oil or canola oil. The specific name for this kind of dietary Vitamin K is phylloquinone, or Vitamin K1. As you can see there are plenty of ways to make sure you have sufficient Vitamin K in your diet. There are also Vitamin K shots, but these are given to newborns because of their sterile GI tract being unable to synthesize Vitamin K right after birth.

## 7.4.2 Functions
### Physiologic Effects of Vitamin K

As its nickname suggests, vitamin K is essential in blood clotting. Vitamin K activates several proteins involved in the clotting. The most notable protein that Vitamin K activates is prothrombin, the precursor to thrombin which in turn becomes fibrin that forms a solid clot. Vitamin K, reduced to Vitamin KH2, activates proteins through carboxylation of glutamic acids. Vitamin K serves as an essential cofactor for a carboxylase that catalyzes carboxylation of glutamic acid residues on vitamin K-dependent proteins. When the carboxylation occurs proteins are able to bind to cell membranes. When binding occurs, it is likely that interaction will also occur; this interaction is what leads to clot formation. Anticoagulation drugs, such as Coumadin and Warfarin, block Vitamin K from being reduced and therefore interrupting the cycle and inhibiting clot formation. The key vitamin K-dependent proteins include:
* proteins: factors II (prothrombin), VII, IX and X
* Anticoagulation proteins: proteins C, S and Z
* Others: bone proteins osteocalcin and matrix-Gla protein, and certain ribosomal proteins

### The Vitamin K Cycle

As a cofactor to the carboxylase that generates gamma-carboxyglutamic acid, Vitamin K undergoes a cycle of oxidation and reduction that allows its reuse. The essential details of this cycle are:
* Vitamin K (usually K1) is reduced to vitamin KH2.
* Oxygenation of vitamin KH2 provides the energy to drive the carboxylation reaction, leading to formation of gamma-carboxyglutamic acid residues and vitamin K oxide.
* Vitamin K oxide is reduced by another reductase back to vitamin K, ready to enter another cycle. Anticoagulants such as Warfarin block the reduction of vitamin K oxide to vitamin K, explaining their antagonistic effects on this cycle.

## 7.4.3 Requirements

Vitamin K is an essential fat-soluble vitamin that is very important in blood clotting, synthesis of bone protein, and preventing hemorrhagic disease. In order to keep all of these functions in check and running properly there are recommendations and requirements that should be met daily. It is extremely important that these requirements are met and or not exceeded. If the daily recommendations are exceeded ad go over the upper limit amount it is very possible that the effectiveness of anti-clotting medications can be compromised or labeled ineffective. The adequate intake (daily recommendation) differentiates for men and women. For men, the adequate intake is 120 micrograms per day. For women, the adequate intake is about 90 micrograms per day. It is also suggested that, “human dietary vitamin K requirement (for its coagulation role) of about 1mg/kg body weight/day,” (WHO), is normal.
When we are born, each and every one of us receives a single dose of vitamin K that is synthesized by the bacteria in the GI tract. The way this occurs is through, “absorption of vitamin K2 from the distal small bowel, supporting a definite role for bacterially synthesized vitamin K2 in contributing to the human nutritional requirements of this vitamin.”(American Journal of Gastroenterology). However, “the amount is insufficient to meet the body’s needs and its bioavailability is limited,” (textbook). Therefore we have to find other sources of vitamin K to keep our body’s systems functioning. You can meet these daily requirements by eating foods such as leafy green vegetables (kale or spinach), some fruit, animal liver (beef liver), or milk. If we as consumers are aware of our personal daily requirements for vitamin K then we can eat the right foods rich in that vitamin and live healthy lives.
Vitamin K is a fat soluble vitamin which means two things: that it is found in the fat and oily parts of food, and that it is stored in the liver and adipose tissue. Since vitamin K is stored in the fatty parts of our body, our bodies store it there longer. Since this essential vitamin is stored longer the daily intake and daily recommendations is not as crucial as it would be with water soluble vitamins, which are not stored as long as fat soluble vitamins. However, just because daily intake of vitamin K and other fat-soluble vitamins is not as crucial does not mean that we completely ignore their importance and the importance of consuming these vitamins and nutrients.

## 7.4.4 Deficiency

Vitamin K deficiency can lead to excessive bleeding, which may begin as oozing from the gums or nose. Other things that may lead to vitamin K deficiency include:
* Health problems that can prevent your body from absorbing vitamin K, such as gallbladder or biliary disease, cystic fibrosis, celiac disease, and Crohn's disease
* Liver disease
* Taking blood-thinners, such as warfarin (Coumadin)
* Long-term hemodialysis
* Serious burns

### Conditions that benefit from vitamin K
#### Excessive Bleeding

Vitamin K is used to reduce the risk of bleeding in liver disease, conditions where your body doesn' t absorb enough vitamin K, or if you taken antibiotics for a long time. Even though vitamin K deficiency in newborns is very rare, it is dangerous enough that doctors give the injections. Newborns at greatest risk for vitamin K deficiency are premature or those whose mother had to take seizure medications during pregnancy. Mothers on seizure medications are often given oral vitamin K for 2 weeks before delivery.

#### Osteoporosis

Your body needs vitamin K to use calcium to build bone. People who have higher levels of vitamin K have greater bone density, while low levels of vitamin K have been found in those with osteoporosis. There is increasing evidence that vitamin K improves bone health and reduces risk of bone fractures, particularly in postmenopausal women who are at risk for osteoporosis. In addition, studies of male and female athletes have also found that vitamin K helps with bone health. However, some studies have found that vitamin K didn' t help with bone density.

## 7.4.5 Toxicity

According to research, excessive intake of natural forms of Vitamin K (Vitamin K1 and Vitamin K2) is unlikely to cause toxicity symptoms (Contreras, 2007). However, another form of Vitamin K, also known as K-3 or menadione, is correlated with detrimentally toxic effects. Because of this, toxicity with the first two forms is uncommon, while there is evidence but little modern research that has investigated the toxicity of Vitamin K in the form of K-3. With that said, a tolerable upper intake level (UL) for natural Vitamin K has yet to be established (Acquilina, Costa, & Wallace, 2014).
The naturally occurring compounds of Vitamin K are K1 (Phylloquinone), and K2 (Menaquinone) (Molitor & Robinson, 1940). As mentioned before, synthetic vitamin K, a form known as K-3 or menadione, is associated with potentially toxic effects in young children, those undergoing synthetic vitamin K-3 injections, or taking supplements that specifically include menadione (Booth, Golly, Sacheck, Roubenoff, Dellal, Hamada, & Blumberg, 2004) .
Because of this, product labels may list Vitamin K-3 in these forms:
* menadione sodium bisulfate
* menadione sodium bisulfite
* menadione dimethylprimidinol sulfate
* menadione dimethylprimidinol sulfite
* menadione dimethylpyrimidinol bisulfite
The ingredients named above may not be directly listed so consumers should look out for key phrases on labels such as “a source of vitamin K activity” or “Vitamin K supplement” (Contreras, 2007). With that said, consumers should be cautious because manufacturers may neglect to include the entire chemical name under ingredient lists due to the potentially toxic effects from synthetic ingredients such as menadione. For example, an ingredient might appear as dimethylprimidinol sulfate instead of its entire chemical name, menadione dimethylprimidinol sulfate.
Natural forms of Vitamin K are fat-soluble; however, menadione derivatives are water-soluble and therefore, circumvent utilization by the body. In addition, the body cannot process menadione in its pure form, allowing it to accumulate and become toxic in the body.
Symptoms of synthetic Vitamin K-3 toxicity can include the following (Acquilina, Costa, & Wallace 2014):
* fatigue
* jaundice (yellow coloring of the skin and eyes)
* hemolytic anemia (the destruction of red blood cells at a faster rate than the bone marrow can produce them)
* hyperbilirubinemia (an excess amount of bilirubin in the blood, causing pigmentation in skin and eyes)
* oral coagulants may become ineffective
* interference with certain medications meant to thin the blood
These symptoms can appear even at acute toxicity levels. Acute levels of toxicity can be reached when levels exceed the daily requirements by a factor of 1000. The United States Food and Drug Administration outlawed the addition of this man-made form of Vitamin K in all over-the-counter nutritional supplements (Booth, Golly, Sacheck, Roubenoff, Dellal, Hamada, & Blumberg, 2004). Synthetic Vitamin K or menadione (K-3) is not recommended to supplement a Vitamin K deficiency. However, there is still controversy regarding the use of menadione in animal feed products due to the unconfirmed data on its supposed benefits and/or detrimental effects.
Vitamin K toxicity is very rare and not something that is overly necessary to worry about. Currently, no harmful side effects have been discovered from having very high intakes of Vitamin K. Because of this, an Upper Level of Vitamin K has not even been established. The only negative side effect that has been discovered is one that is only relevant to those who are taking anticoagulant drugs in order to prevent their blood from clotting. For those people whom this applies to, there is a chance that too much vitamin K could reduce the effectiveness of the drug. This is because one of the main functions of Vitamin K in the body is blood clotting. Appropriately, Vitamin K gets its name from the Danish word koagulation, which, when translated, actually means ‘coagulation’ or ‘clotting’. However, they are able to go about their lives normally and with normal diets. Their blood is monitored regularly and adjustments are made to the doses if needed.
Since the majority of Vitamin K intake comes from the diet, mainly leafy greens, vegetables, fruits, and oils, you can see why there isn’t much of a chance of getting too high levels of Vitamin K. The other source of Vitamin K is a nonfood source in the body produced when bacteria in the GI tract synthesizes Vitamin K. However the amount produced by this is very low and once again, could never cause toxicity.

## References

* ↑ Atkins, Welldon, Wijenayaka, Bonewald, & Findlay, 2009). Vitamin K is rather abundant and having a Vitamin K deficiency is rare (“Vitamin K,” 2013
* ↑ Whitney, E., & Rolfes, S. (2002). Understanding nutrition (9th ed.). Belmont, CA: Wadsworth. (http://ng.cengage.com/static/nb/ui/index.html?nbId=196342&nbNodeId=58604887&deploymentId=4842767387588213997397576#!&parentId=58604888)
* ↑ Vitamin K. (n.d.). Retrieved December 1, 2015, from http://www.webmd.com/vitamins-supplements/ingredientmono-983-vitamin k.aspx?activeingredientid=983&activeingredientname=vitamin k
* ↑ Conly, J. M., Stein, K., Worobetz, L., & Rutledge-Harding, S. (1994). The contribution of vitamin K2 (menaquinones) produced by the intestinal microflora to human nutritional requirements for vitamin K. The American journal of gastroenterology, 89(6), 915-923.
* ↑ Joint, F. A. O., & World Health Organization. (2005). Vitamin and mineral requirements in human nutrition.
* ↑ Whitney, E., Rolfes,S. R.(2013). Understanding Nutrition: 14th Edition. Stamford, CT: Cengage Learning.
* ↑ Whitney, E., & Rolfes, S. (2002). Understanding nutrition (9th ed.). Belmont, CA: Wadsworth. (http://ng.cengage.com/static/nb/ui/index.html?nbId=196342&nbNodeId=58604887&deploymentId=4842767387588213997397576#!&parentId=58604888)
* ↑ Vitamin K. (n.d.). Retrieved December 1, 2015, from http://www.webmd.com/vitamins-supplements/ingredientmono-983-vitamink.aspx?activeingredientid=983&activeingredientname=vitamin k
* ↑ 10 Important Facts About Vitamin K That You Need to Know. (2004, March 24). Retrieved December 1, 2015, from http://articles.mercola.com/sites/articles/archive/2004/03/24/vitamin-k-part-two.aspx