Vitamin K1

Vitamin K1 is a natural supplement belonging to the supplement category of the fat-soluble vitamins class.

Vitamin K1 is also known as phylloquinone or phytonadione.

A deficiency of vitamin K1 can lead to impaired blood clotting, which can increase bleeding tendencies and cause problems with wound healing and coagulation-related diseases.

Vitamin K1 is crucial in synthesizing clotting factors required for blood coagulation and vascular metabolism.

Vitamin K1 is absorbed in the small intestine, which is then transported through the bloodstream, attached to lipoproteins, processed in the liver, and removed through bile and faeces.

The common side effects of vitamin K1 include mild gastrointestinal disturbances, such as nausea, diarrhoea, or stomach cramps.

Vitamin K1 is available in various forms, like tablets and injection emulsions.

Vitamin K1 is a single compound in photosynthetic organisms like cyanobacteria, algae, and green plants. Boiled spinach, asparagus, broccoli, plums, soyabean oil, kidney beans, green and red grapes are natural plant sources of Vitamin K1. Mayonnaise, coleslaw with homemade dressing, and margarine also contain vitamin K1.

Biochemical Action of Vitamin K1

Vitamin K1 belonging to the supplement class, acts as an anticoagulant agent. Vitamin K acts through the vitamin K-dependent pathway.

Vitamin K1 plays a crucial role in blood clotting. It functions as a cofactor for carboxylation, converting carboxyglutamate (GLa) from glutamate residues associated with proteins. Factors II (prothrombin), VII, IX, X, protein C, and protein S are GLa-containing proteins necessary for healthy coagulation. Vitamin K1 activates proteins dependent on vitamin K (VKD), promoting healthy blood clotting and preserving hemostasis. To avoid bleeding disorders and preserve the body's optimal clotting function, consuming enough vitamin K1 through a healthy diet is essential.

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

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

The initial half-life of intravenous phylloquinone is 22 minutes, followed by a half-life of 125 minutes.

Vitamin K1 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 K1 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 K1 supplement is used off-label for intracranial haemorrhage associated with vitamin K antagonist anticoagulants.

Vitamins and natural supplements should not replace a balanced diet

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

Vitamin K1 is a supplement that benefits health in numerous ways.

• Clotting factor: Vitamin K1 is essential for producing clotting factors necessary to stimulate blood clotting and prevent excessive bleeding appropriately. Additionally, it is used to protect newborns from bleeding-related severe hemorrhagic disease. The most effective treatment for hypoprothrombinemia brought on by biliary fistulas or obstructive jaundice is vitamin K1.
• Bone Health: Vitamin K1 supports bone mineralization and calcium homeostasis maintenance, improving bone health and preventing osteoporosis.
• 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 K1 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 destroy free radicals and protect cells from oxidative stress, vitamin K1 has the potential to promote overall well-being. By regulating immune cell development and their response to infections, vitamin K1 enhances healthy immunological function.
• Immune system: Vitamin K1 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 K1 activates this protein. The development of calcium oxalate urolithiasis may be facilitated by decreased carboxylase activity in urolithic patients.

• Orally: All oral solid forms of vitamin K1 are often taken before or after meals, however, it's generally recommended to take atleast 30 minutes on an empty stomach.
• Parenterally: The injectable emulsion of vitamin K1 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 professional.

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

Vitamin K1 is available in various forms, including oral tablets and injection emulsion.

No specific dietary restrictions, but interactions with certain medications may occur.

• Individuals with hypersensitivity to vitamin K1.
• Patients on anticoagulant therapy should use caution and seek medical advice before taking vitamin K1 supplements.

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 K1 in case of allergies.

Due to its fat-soluble nature, vitamin K1 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.

Vitamin K1 supplementation is generally well-tolerated and safe.

The adverse reactions related to vitamin K1 can be categorized as-

• Common: Hypersensitivity reactions, injection site reactions (for injectable formulations).
• Less Common: Allergic reaction like rash, itching or hives
• Rare: Anaphylactic reactions, hemolytic anemia, jaundice, and liver problems like hyperbilirubinemia lead to jaundice.

• Warfarin (Coumadin): Vitamin K1 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 K1 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 K1, 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 K1 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 K1 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 K1. It may shorten the prothrombin time when used with warfarin. Clinicians recommend orlistat users take a vitamin K-fortified multivitamin supplement

• Diarrhea
• Stomach cramps
• Hives
• Breathing difficulty
• Swelling of your face, lips, tongue, or throat.
• Dizziness
• Headache

Vitamin K in Specific Populations

• Pregnancy: The recommended daily intake of oral vitamin K1 is 90 mcg. Pregnant women's clotting function has been demonstrated to be improved, and plasma concentrations of vitamin K1 have been shown to increase when supplementing with pharmacological dosages of vitamin K1 during the final stages of pregnancy, according to certain studies.
• Paediatrics: The recommended daily intake of oral vitamin K1 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 K1 plays a crucial part in the pathophysiology of Alzheimer's disease. The central and peripheral neural systems can have vitamin K1 intake.
• Lactating mothers: The recommended daily intake for lactating mothers is 90 mcg. The diets of nursing women have little effect on the vitamin K1 content of milk. Mothers who are nursing have the same Adequate Intake (AI) for women who are not pregnant since vitamin K1 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

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.

Reversal of Warfarin Effects

Omit 1-2 doses, or hold warfarin; monitor INR and adjust warfarin dose accordingly

INR 4.5-10, no bleeding: 2012 ACCP guidelines suggest against routine use; 2008 ACCP guidelines suggest considering vitamin K1 (phytonadione) 1-2.5 mg PO once

INR >10, no bleeding: 2012 ACCP guidelines recommend vitamin K1 PO (dose not specified); 2008 ACCP guidelines suggest 2.5-5 mg PO once; INR reduction observed within 24-48 hr, monitor INR and give additional vitamin K if needed

Minor bleeding, any elevated INR: Consider 2.5-5 mg PO once; may repeat if needed after 24 hr

Major bleeding, any elevated INR: 2012 ACCP guidelines recommend prothrombin complex concentrate, human (PCC, Kcentra) plus vitamin K1 5-10 mg IV (dilute in 50 mL IV fluid and infuse over 20 min).

Overdosage of Vitamin K1 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 K1 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 K1

Vitamin K1 is a cofactor in the blood coagulation pathway, carboxylating particular glutamate residues in clotting factors II, VII, IX, and X to change them into active versions. Their appropriate role in the production of blood clots depends on this post-translational alteration. The vitamin K epoxide reductase enzyme (VKORC1), which recycles vitamin K1 after each reaction, is responsible for carboxylation. The active clotting factors' gamma-carboxyglutamate (GLa) residues engage with calcium ions to bind them to negatively charged phospholipids on cell surfaces, which starts the clotting process. Osteocalcin, a GLa-containing protein that controls bone mineralization, is another way vitamin K1 affects bone metabolism. The G-protein-coupled receptors, for example, are one type of cell membrane receptor that the GLa-containing proteins interact with to produce their effects. The GLa-containing proteins function as essential components in signal transduction cascades by interacting with particular cell membrane receptors, such as G-protein-coupled receptors.

Kinetic profile:

• Absorption: The proximal part of the small intestine is where vitamin K1 is largely absorbed. For emulsification and absorption, it requires pancreatic lipase and bile salts. After being absorbed, it is combined with chylomicrons, which are large lipoprotein particles, and delivered into the bloodstream via the lymphatic system.
• Distribution: For distribution to different tissues and organs throughout the body, vitamin K1 is primarily attached to lipoproteins, such as VLDL (very low-density lipoprotein) and LDL (low-density lipoprotein).
• Metabolism: The liver processes vitamin K1 through hepatic metabolism. During the carboxylation of clotting factors, it is transformed into vitamin K epoxide, an inactive form. The liver's enzyme vitamin K epoxide reductase (VKORC1) recycles and regenerates active vitamin K1 by converting vitamin K epoxide back to its active form.
• Elimination: Bile and faeces are the main excretion routes for vitamin K1 and its metabolites. Additionally, some vitamin K1 is eliminated in the urine.

1. https://www.ncbi.nlm.nih.gov/books/NBK554545/
2. https://www.ncbi.nlm.nih.gov/books/NBK557622/
3. https://academic.oup.com/nutritionreviews/article/80/4/677/6362591
4. https://downloads.hindawi.com/journals/jnme/2017/6254836.pdf

5. https://www.fssai.gov.in/upload/advisories/2021/07/60f1798019f94Direction_RDA_16_07_2021.pdf

6. National Institute of Nutrition. 2011. Dietary guidelines for Indians; 2nd Edition. Hyderabad. India