Vitamin K

Biochemical action of vitamin K

Vitamin K belonging to the supplement class acts as an anticoagulant agent. Vitamin K acts through the vitamin K-dependent pathway. In this pathway, prothrombin and the clotting factors VII, IX, and X are activated in the liver. Specific glutamate residues in these proteins are carboxylated to create their active versions with vitamin K. This enables the clotting factors to interact with calcium ions and assist in developing stable blood clots, which are essential for hemostasis and wound healing.

Vitamin K is a cofactor for the enzymes that activate the clotting factors necessary for the blood clotting process. It allows it easier for inactive prothrombin to become active thrombin, which causes blood clots to develop.

Vitamin K stimulates proteins that control calcium levels in bone metabolism, ensuring appropriate mineralization of bones and teeth.

Onset: 6-10 hr (PO); 1-2 hr (IV)

Peak effect: 24-48 hr (PO); 12-14 hr (IV)

Vitamin K is available in various forms, like tablets and injection emulsions.

• Tablets: To be swallowed whole with water/liquid, as applicable.
• Injection emulsion: To be administered parenterally, as applicable.

Vitamin K can be used as a supplement for synthesizing several blood coagulation factors.

As a supplement in the treatment and prevention of bleeding disorders and also help in the management of warfarin-induced bleeding.

Vitamin K supplement improves bone health and lowers the risk of osteoporosis.

Vitamins and natural supplements should not replace a balanced diet

Vitamin K is a supplement that benefits health in numerous ways.

• Clotting factor: To properly promote blood clotting and avoid excessive bleeding, vitamin K is crucial for producing clotting components. Additionally, it is utilized to prevent neonates from hemorrhagic disease, which causes significant bleeding. Vitamin K is best for treating irregular blood coagulation caused by hypoprothrombinemia from biliary fistulas or obstructive jaundice.
• Osteoporosis: For strong bones, vitamin K is essential. According to several studies, those who consume more foods high in vitamin K have stronger bones and are less likely to have a hip fracture. By aiding in activating osteocalcin, a protein essential for bone mineralization, adequate vitamin K levels maintain bone health.
• Coronary heart disease: Researchers are investigating whether low vitamin K levels cause heart-feeding blood arteries to tighten and shrink, increasing the risk of coronary heart disease. According to certain studies, vitamin K may help minimize the risk of cardiovascular disease by avoiding arterial calcification and improving artery flexibility.
• Antioxidant properties: As an antioxidant with the ability to fight free radicals and protect cells from oxidative stress, vitamin K has the potential to promote overall well-being. By regulating immune cell development and their response to infections, vitamin K enhances healthy immunological function.
• Immune system: Vitamin K helps the immune system by affecting resistant cell generation and reaction, supporting an overall robust immune system and helping to fight against infections.
• Antidote: Since vitamin K antagonists are employed as rodenticides, they can be utilized as an antidote to treat overshooting or poisoning.
• Renal calculi: Precipitation of calcium salts is avoided by GLa protein in the urine. Through carboxylation, vitamin K activates this protein. The development of calcium oxalate urolithiasis may be facilitated by decreased carboxylase activity in urolithic patients.

• Orally: When taking oral solid forms of vitamin K, eating a meal or snack containing fat is advisable for better absorption.
• Parenterally: The injectable emulsion of vitamin K is aseptically drawn and administered through an intravenous, intramuscular and subcutaneous route.

The dosage and duration of treatment should be as per the clinical judgment of the treating healthcare professionals.

Vitamins and natural supplements should not replace a balanced diet

This product is not intended to diagnose, treat or prevent any disease(s).

• Tablet: 100mcg, 5mg
• Injection emulsion: 2mg/mL, 10mg/mL

Dosage Adjustment in Adult Patients

The oral dose may be repeated in 12-48 hrs, and the SC/IV/IM dose in

6-8 hr if necessary.

Intake of high-dose (10-15 mg) of vitamin K may cause warfarin resistance for ≥1 week.

Hypoprothrombinemia: Due to Drugs or Factors Limiting

Absorption or Synthesis: 2.5 to 10 mg PO/SC; may be increased PRN to 25 mg or, rarely, to 50 mg, it may be repeated in 12-48 hours.

For reversing the warfarin effect, it is advised to omit 1-2 doses or hold warfarin; monitor INR and adjust the warfarin dose accordingly.

Vitamin K is available in various forms, including oral tablets and injection emulsions.

• The advantages of Vitamin K are countered by any meal or drink that contains caffeine, including coffee, tea, chocolate, and soda.
• Limit alcoholic beverages.
• Stay within your daily calorie needs.

The dietary restriction should be individualized as per patient requirements.

Recommended Daily Allowance (RDA)

The RDA for adult men is 120 mcg, and for women is 90 mcg

respectively.

Upper Tolerable Intake (UTL):

No UTL is set for vitamin K, as data concerning adverse effects are insufficient.

• Individuals with hypersensitivity to vitamin K.
• It is contraindicated in newborns with congenital hypoprothrombinemia.
• Contraindicated in Chronic kidney disease (CKD), especially in dialysis patients.
• For individuals receiving excessive heparin-induced anticoagulation, concurrent use of vitamin K may be contraindicated.

The treating healthcare must closely keep a watch and monitor for signs and symptoms like prolonged nausea, vomiting, or stomach discomfort. It is recommended to discontinue vitamin K in case of allergies.

Due to its fat-soluble nature, vitamin K is not easily eliminated from the body; thus, it is essential to follow the recommended dosage since exceeding it may result in difficulties. To prevent interactions, warfarin and other blood thinners should be taken under medical supervision.

Caution is advised when consuming alcohol with vitamin K.

Safe to use during breastfeeding. Several studies suggest that the drug does not pass into the breastmilk significantly and is not harmful to the baby.

There is no sufficient scientific evidence traceable regarding the use and safety of vitamin K in pregnancy.

Vitamin K supplementation is generally well-tolerated and safe.

The adverse reactions related to vitamin K can be categorized as-

• Common: Hypersensitivity reactions, injection site reactions (for injectable formulations).
• Less Common: Nausea, vomiting and diarrhoea.
• Rare: Allergic reactions, hemolytic anaemia, jaundice and liver problems.

• Warfarin (Coumadin): Vitamin K and Warfarin, a medication that helps to prevent blood clots when used concurrently, may decrease the effects of warfarin. Depending on the results of routine blood tests, the warfarin dosage may need to be modified.
• Antibiotics: Antibiotics can potentially reduce the availability of vitamin K in the body by destroying the bacteria in the stomach that produce it. Cephalosporin antibiotics, like cefoperazone, may also limit the body's production of vitamin K, which could cause this impact more prominent.
• Bile acid sequestrants: By inhibiting the reabsorption of bile acids, bile acid sequestrants like cholestyramine and colestipol are used to lower cholesterol levels. Additionally, they can decrease the absorption of vitamin K and other fat-soluble vitamins; however, it is still being determined how clinically significant this impact is. People using these medications should have their vitamin K status monitored, particularly when taken for a long duration of time.
• Orlistat: The weight-loss medication orlistat, which is both over the counter and by prescription, decreases the absorption of dietary fat, including the absorption of fat-soluble vitamins like vitamin K. It may shorten the prothrombin time when used with warfarin. Clinicians recommend orlistat users take a vitamin K-fortified multivitamin supplement.

Common side effects of vitamin K supplementation include:

• Rash
• Itching or swelling)
• Dizziness
• Headache
• Upset stomach
• Hemolytic anemia in high doses

• Pregnancy: The recommended daily intake of oral vitamin K is 90 mcg. Pregnant women's clotting function has been demonstrated to be improved, and plasma concentrations of vitamin K have been shown to increase when supplementing with pharmacological dosages of vitamin K during the final stages of pregnancy, according to certain studies.

• Paediatrics: The recommended daily intake of oral vitamin K in paediatrics ranges from 2-75 mcg/day.

Dosage Adjustment for Paediatric Patients

Hemorrhagic Disease in the Newborn

As Prophylaxis, administer 0.5-1 mg IM within 1 hr of birth.

Treatment with 1 mg/dose/day SC; larger doses of oral anticoagulants may be needed if the mother takes them.

• Geriatrics: With advancing age, cognitive loss is expected. Vitamin K plays a crucial part in the pathophysiology of Alzheimer's disease. The central and peripheral neural systems can have vitamin K intake.

• Lactating mothers: The recommended daily intake for lactating mothers is 90 mcg.The diets of nursing women have little effect on the vitamin K content of milk. Mothers who are nursing have the same Adequate Intake (AI) for women who are not pregnant since vitamin K is not significantly released in milk. According to studies, the medicine is safe for infants and minimally reaches through breast milk.

Dosage Adjustment in Kidney Impairment

There are no specific dosage adjustments provided.

Dosage Adjustment in Hepatic Impairment

There are no specific dosage adjustments provided.

Dosage Adjustment in Adult Patients

The oral dose may be repeated in 12-48 hr, and SC/IV/IM dose in

6-8 hr if necessary.

Intake of high-dose (10-15 mg) of vitamin K may cause warfarin resistance for ≥1 week.

Hypoprothrombinemia: Due to Drugs or Factors Limiting

Absorption or Synthesis; 2.5-10 mg PO/SC; may be increased PRN to 25 mg or, rarely, to 50 mg; may be repeated in 12-48 hours.

For reversing the warfarin effect, it is advised to omit 1-2 doses or hold warfarin; monitor INR and adjust warfarin dose accordingly.

Overdosage of Vitamin K supplements is rare, as it is fat-soluble and cannot easily be excreted by the body. High doses may show symptoms like headache, nausea, diarrhoea and skin rashes, which are self-limiting.

There is no specific treatment that is recommended in the event of an overdose. When an overdose is suspected, vitamin K should be terminated immediately. Supportive therapy should also be given, addressing any symptoms that persist or worsen. Physical treatment might be added if necessary.

Biochemistry profile of vitamin K

The naphthoquinone ring in the structure of vitamin K, which determines its many forms (K1, K2, K3), has a variable aliphatic side chain. It is essential for healthy bone development and blood clotting. Specific glutamyl residues in a limited amount of proteins, including prothrombin and coagulation factors VII, IX, and X, must be converted -carboxy glutamyl (Gla) residues for this process to occur. Prothrombin time increases, and, in severe cases, hemorrhagic events arise due to under-carboxylated forms of these proteins that result from a vitamin K deficiency. The vitamin K-dependent proteins, like osteocalcin and matrix Gla protein, have received attention due to their role in preventing chronic illnesses. There hasn't been any evidence to establish a connection between disease-related physiological responses and the reduced biological activity of other vitamin K-dependent proteins, nevertheless. These findings emphasize vitamin K's crucial significance in preserving healthy protein function and its potential effects on health beyond blood clotting control.

Kinetic profile:

• Absorption: Most vitamin K is absorbed from the proximal small intestine. It depends on healthy pancreatic and bile flow and is enhanced better by dietary fat.
• Distribution: Following ingesting, vitamin K enters the circulation and is carried by lipoproteins throughout the body. It is transferred to multiple organs, including the liver, producing proteins that depend on vitamin K, such as clotting factors.
• Metabolism: Vitamin K is activated by enzymatic processes in the liver, converting it from an inactive form to an active state. Specific glutamyl residues in clotting factors are carboxylated by the active form of vitamin K, forming -carboxyglutamate (Gla) residues.
• Excretion: A relatively small amount of vitamin K is excreted in the urine. Vitamin K and its metabolites are mostly excreted via bile into the faeces.

1. https://www.ncbi.nlm.nih.gov/books/NBK554545/
2. https://academic.oup.com/nutritionreviews/article/80/4/677/6362591#337988540
3. https://ods.od.nih.gov/factsheets/VitaminK-HealthProfessional/
4. https://www.ncbi.nlm.nih.gov/books/NBK222299/
5. https://www.ncbi.nlm.nih.gov/books/NBK551578/#:~:text=Vitamin K use requires caution,and hypersensitivity to vitamin K.