Vitamin K plays an essential role in liver function, primarily through its involvement in synthesising clotting factors that prevent excessive bleeding. The liver produces several vitamin K-dependent proteins, including coagulation factors II, VII, IX, and X, which are critical for normal haemostasis. Patients with liver disease may develop vitamin K deficiency due to impaired bile flow, malabsorption, or poor dietary intake, leading to coagulopathy and increased bleeding risk. Understanding the relationship between vitamin K and liver health is important for managing patients with hepatic conditions, particularly those with cholestatic disease or cirrhosis.

How Vitamin K Supports Liver Function

Vitamin K plays a crucial role in maintaining normal liver function, primarily through its involvement in the synthesis of clotting factors. The liver produces several vitamin K-dependent proteins, including coagulation factors II (prothrombin), VII, IX, and X, as well as anticoagulant proteins C and S. These factors are essential for the blood clotting cascade, which prevents excessive bleeding following injury.

The mechanism by which vitamin K supports these processes involves a specific enzyme called gamma-glutamyl carboxylase. This enzyme requires vitamin K as a cofactor to activate clotting factors through a process called carboxylation. During this reaction, vitamin K is converted from its reduced form (hydroquinone) to its oxidised form (epoxide). The liver then recycles vitamin K epoxide back to its active form through the vitamin K epoxide reductase (VKOR) enzyme, creating a continuous cycle known as the vitamin K cycle.

Beyond coagulation, some preliminary research suggests vitamin K may have additional hepatoprotective properties. Some laboratory and animal studies indicate that vitamin K2 (menaquinone) might help reduce inflammation and oxidative stress in liver tissue, though these findings remain investigational and have not been established in clinical practice. It is important to note that whilst vitamin K is essential for liver-dependent clotting factor synthesis, there is no established evidence supporting vitamin K supplementation as a treatment for primary liver disease itself.

Patients with healthy liver function typically maintain adequate vitamin K status through dietary intake and intestinal bacterial synthesis. The recommended daily intake for adults in the UK is approximately 1 microgram per kilogram of body weight, as advised by the NHS. This can be easily achieved through a balanced diet including green leafy vegetables, vegetable oils, and certain fermented foods.

Importantly, patients taking warfarin should not start vitamin K supplements or significantly change their dietary vitamin K intake without consulting their healthcare provider, as this could interfere with anticoagulation control.

Monitoring Vitamin K Levels in Liver Patients

Direct measurement of vitamin K levels is not routinely performed in clinical practice, as the tests are expensive, not widely available, and do not always correlate with functional vitamin K status. Instead, healthcare professionals typically assess vitamin K function indirectly by measuring the prothrombin time (PT) and its standardised derivative, the International Normalised Ratio (INR). These tests evaluate how quickly blood clots and reflect the activity of vitamin K-dependent clotting factors.

In patients with liver disease, an elevated PT/INR may indicate either impaired hepatic synthesis of clotting factors (due to liver dysfunction) or vitamin K deficiency, or both. To distinguish between these causes, clinicians may administer a trial of vitamin K supplementation—typically 5-10 mg of phytomenadione (vitamin K1) given orally or by slow intravenous injection. If the PT/INR improves significantly within 24–48 hours, this suggests vitamin K deficiency was contributing to the coagulopathy. Conversely, minimal or no response indicates that the liver's synthetic capacity is too compromised to produce clotting factors even when adequate vitamin K is available.

It is important to note that in cirrhosis, the INR does not reliably predict bleeding risk, as the haemostatic system is rebalanced with reductions in both pro- and anti-coagulant factors. Monitoring frequency should be individualised based on specialist assessment of disease severity and clinical context.

Patients should be advised to seek urgent medical attention for any signs of significant bleeding, including:

• Vomiting blood or material that looks like coffee grounds

• Passing black, tarry stools

• Unexplained bruising or petechiae

• Prolonged bleeding from minor cuts

• Bleeding gums

• Blood in urine or stools

• Unusually heavy menstrual periods

For severe bleeding (particularly vomiting blood or passing black stools), patients should call 999 or go to A&E immediately, as these may indicate life-threatening haemorrhage requiring urgent intervention.

Vitamin K Deficiency and Liver Disease

Vitamin K deficiency commonly occurs in patients with liver disease through several interconnected mechanisms. Cholestatic liver conditions, such as primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), impair bile flow into the intestine. Since vitamin K is a fat-soluble vitamin requiring bile salts for absorption, reduced bile secretion leads to malabsorption and subsequent deficiency. Some patients with advanced liver disease may also have fat malabsorption due to coexisting conditions such as alcohol-related pancreatic insufficiency or small intestinal bacterial overgrowth.

Dietary insufficiency represents another important contributor. Patients with advanced liver disease frequently experience poor appetite, nausea, and dietary restrictions (such as low-sodium diets), which may limit intake of vitamin K-rich foods. Additionally, alcohol-related liver disease is associated with overall nutritional deficiency, including inadequate vitamin K consumption. Certain medications commonly used in liver disease management, particularly broad-spectrum antibiotics, can reduce intestinal bacterial synthesis of vitamin K2, though dietary vitamin K1 remains the primary source for most individuals.

The clinical consequences of vitamin K deficiency in liver disease extend beyond coagulopathy. Patients may present with easy bruising, mucosal bleeding (epistaxis, gingival bleeding), or more serious haemorrhagic complications. It is essential to recognise that vitamin K deficiency-related bleeding differs from bleeding due to portal hypertension (such as variceal haemorrhage), though both may coexist in advanced liver disease.

Management of vitamin K deficiency in liver disease typically involves oral supplementation with phytomenadione 5-10 mg daily for patients who can absorb oral medications. For those with severe cholestasis or malabsorption, slow intravenous administration may be necessary. Patients with advanced or prolonged cholestatic liver disease should be assessed for fat-soluble vitamin deficiencies, including vitamin K, with supplementation provided if deficiency is confirmed or strongly suspected.

Patients should be counselled about incorporating vitamin K-rich foods into their diet, including kale, spinach, broccoli, and Brussels sprouts, whilst being mindful of any dietary restrictions related to their liver condition. Those taking warfarin should maintain consistent vitamin K intake and avoid starting supplements without medical advice.

Vitamin K in Liver Cirrhosis and Clotting Disorders

Liver cirrhosis presents a complex haemostatic challenge, characterised by a delicate balance between pro-haemorrhagic and pro-thrombotic tendencies—a concept termed 'rebalanced haemostasis'. Whilst cirrhotic patients commonly exhibit prolonged PT/INR suggesting bleeding risk, they simultaneously have reduced levels of natural anticoagulants (proteins C and S), which are also vitamin K-dependent. This creates a precarious equilibrium that can tip towards either bleeding or thrombosis.

In cirrhotic patients, vitamin K administration requires careful consideration. Routine vitamin K supplementation is not universally recommended for all cirrhotic patients with elevated INR, as the coagulopathy primarily reflects reduced hepatic synthetic function rather than vitamin K deficiency alone. However, vitamin K should be administered when deficiency is suspected (particularly in cholestatic cirrhosis or malnutrition) or before selected high-risk invasive procedures.

Importantly, UK guidance recognises that INR does not reliably predict bleeding risk in cirrhosis. For low-risk procedures such as diagnostic or therapeutic paracentesis, prophylactic correction of abnormal INR is not routinely required. Before higher-risk procedures, management should be guided by specialist hepatology input and, where available, viscoelastic testing (TEG/ROTEM) rather than INR alone. If correction is deemed necessary, phytomenadione (5-10 mg orally or by slow intravenous injection) may be given. In cases of active bleeding or for urgent high-risk procedures where INR remains significantly elevated despite vitamin K, prothrombin complex concentrate (PCC) may be preferred over fresh frozen plasma (FFP), though both carry risks including volume overload and transfusion reactions.

Patients with cirrhosis should be advised to:

• Avoid non-steroidal anti-inflammatory drugs (NSAIDs) and aspirin unless specifically prescribed

• Avoid alcohol completely

• Seek immediate medical attention for any bleeding (call 999 or go to A&E for vomiting blood or passing black stools)

• Inform all healthcare providers about their liver condition before any procedure

• Maintain adequate nutrition, including vitamin K-rich foods

For patients on anticoagulation therapy (such as warfarin) who develop liver disease, management becomes particularly challenging. Warfarin inhibits vitamin K epoxide reductase, and its effect is unpredictable in liver disease due to altered drug metabolism and baseline coagulopathy. Direct oral anticoagulants (DOACs) may be considered as alternatives in some cases, but several are contraindicated or not recommended in moderate-to-severe hepatic impairment according to their product information. All patients with cirrhosis requiring anticoagulation should be managed by specialist hepatology and haematology services.

Patients who experience side effects from vitamin K or any medication should report these through the MHRA Yellow Card scheme.

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