Vitamin K1, also known as phylloquinone or phytomenadione, is a fat-soluble vitamin essential for normal blood clotting and bone health. Predominantly obtained through dietary sources such as green leafy vegetables, vitamin K1 plays a critical role in activating clotting factors and preventing bleeding disorders. In clinical practice, it is used to prevent haemorrhagic disease in newborns, reverse warfarin over-anticoagulation, and treat deficiency states caused by malabsorption conditions. Understanding its mechanism, therapeutic applications, and safety profile is vital for healthcare professionals and patients managing anticoagulation therapy or vitamin deficiencies.

What Is Vitamin K1 and How Does It Work?

Vitamin K1, also known as phylloquinone or phytomenadione, is a fat-soluble vitamin essential for normal blood clotting and bone health. It is the primary dietary form of vitamin K, naturally occurring in green leafy vegetables such as spinach, kale, broccoli, and Brussels sprouts. While vitamin K2 (menaquinone) can be produced by bacteria in the gut and found in fermented foods, this contribution is relatively small and variable; vitamin K1 is predominantly obtained through diet and is the form most commonly used in medical supplementation and treatment.

The mechanism of action of vitamin K1 centres on its role as a cofactor for the enzyme gamma-glutamyl carboxylase. This enzyme is responsible for the post-translational modification of specific proteins, converting glutamate residues to gamma-carboxyglutamate (Gla). This carboxylation process is crucial for the activation of several clotting factors, including factors II (prothrombin), VII, IX, and X, as well as proteins C and S, which regulate coagulation. Without adequate vitamin K1, these proteins remain inactive, leading to impaired blood clotting and increased bleeding risk.

Beyond haemostasis, vitamin K1 also activates proteins involved in bone metabolism, particularly osteocalcin, which helps bind calcium to the bone matrix. This contributes to bone mineralisation and skeletal health. The vitamin undergoes a cycle of oxidation and reduction in the body—the vitamin K epoxide cycle—which allows it to be reused multiple times. Certain medications, notably warfarin, inhibit this cycle by blocking vitamin K epoxide reductase (VKORC1), which is why vitamin K1 is used as an antidote in cases of warfarin overdose or excessive anticoagulation.

Importantly, vitamin K1 does not reverse the anticoagulant effects of direct oral anticoagulants (DOACs) such as apixaban or rivaroxaban, which work through different mechanisms.

Uses and Benefits of Vitamin K1

Vitamin K1 has several important clinical applications, both therapeutic and preventative. The most established use is in the prevention and treatment of vitamin K deficiency bleeding (VKDB), particularly in newborns. The UK follows guidance from the Department of Health recommending that all newborns receive prophylactic vitamin K1 shortly after birth, typically as a single intramuscular injection of 1 mg, to prevent haemorrhagic disease of the newborn. Preterm or low-birthweight infants and those with additional risk factors (such as maternal enzyme-inducing antiepileptic drugs or cholestasis) may require adjusted dosing regimens. This practice has dramatically reduced the incidence of early, classical, and late VKDB.

In adults, vitamin K1 is used to reverse warfarin anticoagulation in cases of over-anticoagulation (elevated INR) with or without bleeding. The British Society for Haematology provides guidance on dosing based on INR levels and clinical presentation. For example, patients with an INR above the therapeutic range but without bleeding may require dose omission and monitoring, whilst those with major bleeding require immediate intravenous vitamin K1 (typically 5 mg) alongside prothrombin complex concentrate. Local hospital protocols should always be followed. It is important to note that vitamin K1 does not reverse the effects of direct oral anticoagulants (DOACs).

Vitamin K1 supplementation is also indicated in conditions causing malabsorption of fat-soluble vitamins, such as:

• Coeliac disease

• Crohn's disease and other inflammatory bowel conditions

• Chronic pancreatitis

• Biliary obstruction or cholestatic liver disease

• Cystic fibrosis

Patients on long-term antibiotics that disrupt gut flora, or those with inadequate dietary intake, may also benefit from supplementation. Certain medications, such as cholestyramine and orlistat, can reduce vitamin K absorption and may increase requirements. Emerging research suggests potential roles in bone health and cardiovascular protection, though evidence remains inconclusive and insufficient to recommend routine supplementation for these purposes.

While dietary vitamin K1 supplements are available without prescription, patients taking warfarin should not start vitamin K supplements without medical advice. Therapeutic doses for medical conditions should be prescribed and monitored by healthcare professionals.

Side Effects and Safety Considerations

Vitamin K1 is generally well-tolerated when used appropriately, with serious adverse effects being rare. The most common side effects relate to the route of administration. Intramuscular or intravenous injection may cause local reactions including pain, swelling, bruising, or haematoma at the injection site. Intravenous administration carries a small risk of anaphylactoid reactions, characterised by flushing, dyspnoea, chest tightness, or hypotension. For this reason, intravenous vitamin K1 should be administered as a slow IV injection or infusion according to the product's Summary of Product Characteristics (SmPC), and only when clinically necessary, with resuscitation facilities available.

Oral vitamin K1 is associated with minimal side effects, though gastrointestinal disturbances such as nausea or upset stomach may occasionally occur. Allergic reactions to oral formulations are uncommon but possible. Patients should be advised to report any signs of hypersensitivity, including rash, itching, or difficulty breathing. Seek immediate medical attention (call 999 or attend A&E) if experiencing symptoms of severe allergic reaction or significant bleeding.

An important consideration is the interaction between vitamin K1 and anticoagulant therapy. Patients taking warfarin require careful monitoring, as vitamin K1 directly antagonises warfarin's effect. Sudden increases in dietary vitamin K1 intake (e.g., consuming large amounts of green leafy vegetables) can reduce warfarin efficacy and increase thrombotic risk. Conversely, patients should maintain consistent vitamin K1 intake rather than avoiding it entirely. INR monitoring is particularly important when starting or stopping antibiotics in people on warfarin, as this can affect vitamin K levels. Medications such as cholestyramine and orlistat can reduce vitamin K absorption and may affect anticoagulation control.

There is no established upper tolerable limit for vitamin K1, as toxicity from excessive intake has not been documented. Pregnant and breastfeeding women can safely use vitamin K1 at recommended doses, and it is classified as safe during pregnancy when clinically indicated.

Patients are encouraged to report any suspected adverse reactions to medicines via the MHRA Yellow Card Scheme (www.mhra.gov.uk/yellowcard).

Vitamin K1 Dosage and Administration

Dosing of vitamin K1 varies considerably depending on the clinical indication, severity of deficiency, and patient factors. For neonatal prophylaxis, the standard UK recommendation is a single intramuscular dose of 1 mg given shortly after birth. Parents who decline intramuscular administration may opt for oral dosing, though this requires multiple doses: 2 mg at birth, followed by 2 mg at 4–7 days, and a further 2 mg at 4–6 weeks for breastfed infants. Formula-fed infants may not require the third dose as formula is supplemented with vitamin K. Preterm or low-birthweight infants may require adjusted dosing regimens.

For warfarin reversal, dosing is stratified by INR level and bleeding status, following British Society for Haematology guidelines:

• INR 5.0–8.0 without bleeding: Withhold 1–2 warfarin doses; consider 1–2 mg oral vitamin K1 if high bleeding risk

• INR >8.0 without bleeding: Withhold warfarin; give 1–5 mg oral vitamin K1

• Major bleeding: Stop warfarin; give 5 mg intravenous vitamin K1 slowly, plus prothrombin complex concentrate

Local hospital protocols should always be followed. Importantly, vitamin K1 does not reverse the effects of direct oral anticoagulants (DOACs).

For treatment of vitamin K deficiency in adults with malabsorption, typical initial dosing is 10 mg orally or by slow intravenous injection, with repeat doses based on response and INR monitoring. Maintenance dosing in chronic malabsorption should be tailored to individual needs. Patients with cholestatic liver disease or fat malabsorption may require parenteral administration to ensure adequate absorption. Monitoring should include assessment of clotting function (prothrombin time/INR) to evaluate response.

Dietary reference values for vitamin K1 in the UK suggest adequate intake of approximately 1 microgram per kilogram body weight daily for adults (roughly 65–80 micrograms daily). This is easily achieved through a balanced diet including green vegetables, vegetable oils, and some fruits.

Patients should be advised that fat-soluble vitamin absorption is enhanced when taken with dietary fat. Those with persistent malabsorption may require ongoing supplementation and regular monitoring. Seek urgent medical attention (call 999 or attend A&E) for severe bleeding. Contact your GP or anticoagulation clinic promptly if experiencing unexplained bleeding, easy bruising, or prolonged wound healing, as these may indicate vitamin K deficiency requiring investigation and treatment.

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