What Is Vitamin K Therapy?
Vitamin K is also called coagulation vitamin. It belongs to one kind of vitamins and has chlorophyll quinone bioactivity. It was first discovered and extracted by Danish chemist Dam from animal liver and sesame oil in 1929. Vitamin K includes several forms such as K 1 , K 2 , K 3 , and K 4. Among them, K 1 and K 2 are naturally occurring and belong to fat-soluble vitamins; and K 3 and K 4 are artificially synthesized and are water-soluble. Of vitamins. The chemical properties of the four vitamins K are relatively stable, and they are resistant to acids and heat. They are rarely lost in normal cooking, but they are sensitive to light and easily decomposed by alkali and ultraviolet light [1] .
Vitamin K is also called coagulation vitamin. It belongs to one kind of vitamins and has chlorophyll quinone bioactivity. It was first discovered and extracted by Danish chemist Dam from animal liver and sesame oil in 1929. Vitamin K includes several forms such as K 1 , K 2 , K 3 , and K 4. Among them, K 1 and K 2 are naturally occurring and belong to fat-soluble vitamins; and K 3 and K 4 are artificially synthesized and are water-soluble. Of vitamins. The chemical properties of the four vitamins K are relatively stable, and they are resistant to acids and heat. They are rarely lost in normal cooking, but they are sensitive to light and easily decomposed by alkali and ultraviolet light [1] .
Vitamin K has some physiological functions such as preventing bleeding diseases in newborn babies, preventing internal bleeding and hemorrhoids, reducing heavy bleeding during the physiological period, and promoting normal blood coagulation [2] .
- Chinese name
- Vitamin k
- Foreign name
- Vitamin K
- nickname
- Menadione
- CAS
- 12001-79-5
- EINECS
- 234-408-7
- Molecular weight
- 450.6957
- main application
- For clinical bleeding disorders
Vitamin K Discovery
In 1895, Danish biochemist Carl Peter Henrik Dam was born in Copenhagen, and obtained his Ph.D. from the University of Copenhagen in 1934. [3]
Since 1928, Dam has performed a series of experiments on cholesterol metabolism. Many mammals synthesize cholesterol easily, and he believes chicks lack this ability. For chickens lacking cholesterol in captivity, rich vitamins A and D were added to the feed, and bleeding and bleeding control began after a few weeks [3] .
In 1932, scientists in California believed that this phenomenon was due to a lack of vitamin C, but it was not effective after adding pure vitamin C. [3]
In 1934, Darm believed that an unknown element was lacking in feed and found that this element was soluble in fat [3] .
In 1935, Dam announced the discovery of a new vitamin and called it a "clotting vitamin," or vitamin K. Its best sources were green leaves, tomatoes, and pork liver. K is the first letter of the word "Koagulation" in Scandinavian and German. This substance is fat-soluble [3] .
In 1938, Dam discovered that patients with obstructive jaundice had a tendency to bleed and were also caused by vitamin K deficiency [3] .
In 1939, Darm purified fat-soluble vitamin K from alfalfa. Vitamin K isolated from green plants is called K1, and vitamin K produced by the intestinal putrefaction is called K2. The two are slightly different. The difference was first attributed to the American chemist Edward Adelbert · Edward A. Doisv observed [3] .
In 1940, Doyce first synthesized vitamin K and determined its chemical formula. To this end, Dam and Doise won the 1943 Nobel Prize in Physiology or Medicine [3] .
Vitamin K Biochemical Research
Vitamin K structural properties
Figure 1 Structural formula of vitamin K [1]
Vitamin K is a naphthoquinone compound having an isoprene side chain, and contains vitamin K 1 , vitamin K 2 , vitamin K 3 and vitamin K 4 . Among them, vitamin K 1 and vitamin K 2 are natural. In terms of chemical structure, vitamin K 1 and vitamin K 2 are derivatives of 2-methyl-1,4-naphthoquinone, and the difference is only in the R group. Among them, vitamin K 1 is a yellow oily substance, and K 2 is a pale yellow crystal, both of which are heat resistant, but are easily damaged by ultraviolet radiation, so they should be stored protected from light. Vitamin K 3 and vitamin K 4 are artificially synthesized. Among them, K 3 is 2-methyl 1,4 naphthoquinone, which has a special odor. Vitamin K 4 is a hydroquinone type of K 3. Their properties are better than K 1 And K 2 is stable, and soluble in water, can be used for oral or injection. The molecular structures of the above four are shown in the figure to the right [1] .
Vitamin K biochemical effect
Figure 2 Vitamin K coagulation
1. Participate in the synthesis of Y-carboxyglutamic acid
Vitamin K is an essential substance for the synthesis of four coagulation proteins (prothrombin, transition acceleration factor, anti-hemophilia factor, and stubborn factor) in the liver, and has an auxiliary effect on the synthesis of -carboxyglutamic acid. Without vitamin K, the above-mentioned four coagulation factors synthesized by the liver are abnormal protein molecules, and their ability to catalyze coagulation will be greatly reduced [4] [5] .
The synthesis of -carboxyglutamic acid (-Carboxyglutamic Acid, Gla) is generally performed in the body of cell microparticles, and a peptide chain containing glutamic acid is required as a matrix, and oxygen and carbon dioxide and vitamin K hydroquinone (vitamin KH 2 ) are required. Changes in vitamins in this role can be represented by the vitamin K-vitamin K 2 and K 3 epoxy compounds (vitamin K- 2 , 3epoxide, VKO) cycle [4] [5] .
2. Participate in bone metabolism
In addition to assisting in the synthesis of coagulation proteins, vitamin K also helps bone metabolism. The reason is that vitamin K is involved in the synthesis of BGP (vitamin K-dependent protein), which can regulate the synthesis of calcium phosphate in bones. Especially for the elderly, their bone density and vitamin K are positively correlated. Regular intake of vitamin K-containing green vegetables can effectively reduce the risk of fractures [6] .
Vitamin K absorption and metabolism
Vitamin K can be obtained from food, or it can be synthesized and artificially synthesized by intestinal bacteria. Among them, vitamin K 1 and vitamin K 2 are fat-soluble vitamins, which require bile and pancreatic juice for absorption, are combined with chylomicrons, are absorbed by the small intestine into the lymphatic system, and are transported through the lymphatic system. Its absorption depends on the function of the pancreas and gallbladder, and under normal circumstances, about 40-70% of the intake can be absorbed. Its half-life in the human body is relatively short, about 17 hours [5] .
Humans or animals take physiological or pharmacological doses of vitamin K 1 orally. Vitamin K 1 has appeared in plasma after 20 minutes, and peaks in 2 hours. Within 48 to 72 hours, the plasma concentration decreases exponentially to 1 to 5 ng / ml. During this time, vitamin K1 is transferred from chylomicrons to beta lipoprotein, transported into the liver, combined with very low density lipoprotein (VLDL), and passed through low density lipoprotein (LDL) to tissues. The liver is the main target tissue of vitamin K1. One hour after vitamin K injection, 50% of the dose is in the liver [5] [4] .
After oral administration of vitamin K for 2 hours, the 20% dose was in the liver, which decreased to the lowest value within 24 hours, while the amount of kidney, heart, skin, and muscle increased to the highest value within 24 hours and then decreased. The content of vitamin K in rat liver is about 8-44 ng / g. If the liver concentration is lower than 4.5 ng / g, prothrombin time is prolonged, and the overall vitamin K pool is relatively small, about 50-100 g, and the conversion rate is fast. The overall library can be converted every 2.5 hours. Its metabolites are vitamin K short chains and oxidative metabolites to form -lactones, which can also be combined with glucuronide [5] .
On the side chain of human vitamin K, or can be oxidized to form 6-carboxylic acid and its -lactone or further decomposed into 4-carboxylic acid. Combined, exists in the enterohepatic circulation, or is excreted from the urine [5] .
The artificially synthesized water-soluble vitamin K is more beneficial to human body absorption, and has been widely used in medicine. For example, vitamin K3 is converted to MK 4 in animal liver microsomes, which is only 0.05 to 1.0% of the intake. Its main metabolite is the sulfate of dihydrovitamin K 3 glucuronide [5] .
Vitamin K physiological function
Vitamin K promotes blood clotting
Vitamin K is a coenzyme of the coagulation factor -carboxylase and an essential substance for the synthesis of coagulation factors 2, 7, 9, and 10. The lack of vitamin K in the body will prolong the clotting time, and in severe cases, it will cause bleeding to stop and even death. For women, vitamin K can reduce heavy bleeding during the physiological period, and can also prevent internal bleeding and hemorrhoids. People with frequent nosebleeds may also consider taking more vitamin K from food [7] .
Vitamin K is involved in bone metabolism
Vitamin K is a promoter of bone formation. Clinical and experimental results have shown that it has a clear anti-osteoporosis effect, but its effect is inferior to that of estrogen, and its therapeutic effect is obviously dose-dependent. At present, vitamin K can improve the state of middle-aged and elderly patients with osteoporosis, thereby achieving an anti-osteoporosis effect [8] .
Clinical significance of vitamin K
Healthy people have low requirements for vitamin K and more in their diet, and primary vitamin K deficiency Figure 3 Biochemical effects of vitamin K
Uncommon, clinically visible manifestations due to vitamin K deficiency are secondary bleeding such as wound bleeding, large subcutaneous bleeding, and central nervous system bleeding.
The placenta has a small amount of vitamin K, and the low body storage of the newborn and the sterility of the intestine in the body prevent the use of vitamin K. The content of vitamin K in breast milk is low, the milk intake of the newborn is low, and the immature liver of the baby cannot Hypoprothrombin is common in newborns and babies due to the synthesis of normal amounts of coagulation factors.
It is known that the most common vitamin K deficiency bleeding in adults occurs in patients who take a diet low in vitamin K and take antibiotics. Vitamin K deficiency can be seen in malabsorption syndrome and other gastrointestinal diseases such as cystic fibrosis, mouth Inflammatory diarrhea, ulcerative colitis, segmental enteritis, short bowel syndrome, biliary obstruction, pancreatic insufficiency, etc. All of the above situations require routine supplementation of vitamin K preparations.
Lack of vitamin K reduces prothrombin synthesis in the body, leading to prolonged bleeding time. It will lead to prolonged clotting time and more bleeding, and even minor trauma or contusion may cause blood vessel rupture. Subcutaneous hemorrhage and bleeding or hematuria, anemia and even death of muscles, brain, gastrointestinal tract, abdominal cavity, urogenital system and other organs or tissues. Such as: neonatal hemorrhagic diseases, such as bleeding from the vomiting, intestines, umbilical cord and foreskin; abnormal coagulation in adults, leading to symptoms such as nosebleeds, hematuria, gastric bleeding and stasis; hypothrombin, symptoms are prolonged blood clotting time Subcutaneous bleeding; chronic enteritis in children; tropical diarrhea [2] .
Vitamin K sources and intake
Vitamin K intake sources
There are two sources of human vitamin K: Figure 4 Schematic diagram of vitamin sources
Cheng, mainly K 2 , accounts for 50 to 60%. Vitamin K is absorbed in the ileum. Bacteria must be synthesized in the ileum to be used by the human body. Some antibiotics inhibit the growth of the bacteria in the digestive tract and affect the intake of vitamin K. On the other hand, from the food, it is mainly K 1 , which accounts for 40-50%. The content of green leafy vegetables is high, followed by milk and meat, and the content of fruits and cereals is low [4] .
Since vitamin K is not listed in the Chinese food ingredient list, only the data sheet of the US food ingredient is provided for reference.
Chloroquinone content in common foods in the United States (mg / 100g)
| Food name | Chlorophyll content | Food name | Chlorophyll content |
|---|
spinach | 380 | Dried lentils | twenty two |
lettuce | 315 | liver | 5 |
cabbage | 145 | egg | 2 |
asparagus | 60 | Fresh meat | <1 |
Beans | 33 | Fresh fish | <1 |
pea | twenty four | Whole milk | <1 |
cucumber | 20 | Soybean oil | 193 |
broccoli | 20 | Cottonseed oil | 60 |
carrot | 10 | olive oil | 55 |
tomato | 6 | Corn oil | 3 |
potato | 1 | Vegetable butter | 42 |
Dried soy beans | 47 | cream | 7 |
Recommended Vitamin K Daily
Infants assume that there is no bacteria in the intestine that can synthesize vitamin K. It is recommended to consume 2 g per kilogram of body weight from food. The average adult consumes about 10 g to 20 g per kilogram of body food a day. [7] . See the following table:
| Group | age) | Vitamin K (micrograms) |
|---|
baby | 0-1 | 10 ~ 20 |
child | 1-11 | 11 ~ 60 |
teens | > 11 | 50 ~ 100 |
adult | | 60 ~ 80 |
Vitamin K Requirement
Vitamin K deficiency is uncommon in the normal population, so formulations of vitamin K are commonly used in several groups of people [9] :
1. Those with frequent nosebleeds;
2. People with severe burns or trauma;
3. Those who are taking antibiotics;
4, premature babies, vitamin K can make the blood circulation in the newborn normal;
5. Those who lack enough bile to absorb fat (need to be replenished by injection);
6. Patients with chronic cholecystitis;
7. Long-term application of antibiotics and intestinal sterilization drugs;
8. Patients with pancreatic disease, patients with bile duct disease and small intestinal mucosal atrophy or fat stool.
Vitamin K precautions
1. It will damage liver function and should not be taken by patients with liver disease [10] ;
2. Pregnant women and lactating women avoid taking vitamin K supplements in large quantities [10] ;
3. X-rays, radiation, freeze processing, aspirin, and air pollution all have an inhibitory effect on vitamin K supplements [11] ;
4. If antibiotics are used, the amount of bacteria in the intestine will be reduced or the function will be reduced, and vitamin K will be relatively insufficient [11] ;
5. Simultaneous intake of vitamin K (even if the source is natural foods) will have adverse effects on the anti-blood coagulant properties [11] ;
6. After taking vitamin K supplements, if you have allergic symptoms such as flushing, redness, gastrointestinal discomfort, skin maintenance, etc., you should stop using it immediately and ask your doctor for treatment [11] .
7. Vitamin K 2 in excess of the pharmacological dose can cause hemolytic anemia, hyperbilirubinemia, and liver poisoning in newborns, and can induce heart disease and lung disease in adults.
