Vitamin K2, or menaquinone, is a fat-soluble vitamin essential for calcium metabolism and blood clotting. Unlike vitamin K1, which primarily supports hepatic clotting factors, vitamin K2 demonstrates greater activity in bone and vascular tissues by activating proteins that regulate calcium deposition. This article explores the mechanisms, dietary sources, potential health benefits, and supplementation considerations for vitamin K2, with particular attention to bone health, cardiovascular research, and important safety guidance for patients taking anticoagulant medications.

What Is Vitamin K2 and How Does It Work?

Vitamin K2, also known as menaquinone, is a fat-soluble vitamin that plays a crucial role in calcium metabolism and blood clotting. While vitamin K1 (phylloquinone) is predominantly found in green leafy vegetables and has a primary role in blood clotting, vitamin K2 appears to have greater activity in extrahepatic tissues, particularly bone and vascular systems.

The vitamin K family comprises several subtypes, with K2 existing in multiple forms designated as MK-4 through MK-13, based on the length of their side chains. MK-4 (menatetrenone) and MK-7 are the most clinically studied forms. MK-4 has a shorter half-life of approximately one to two hours, whilst MK-7 remains in circulation for longer (approximately 2-3 days), allowing for more sustained biological activity.

Mechanism of action: Vitamin K2 functions as a cofactor for the enzyme gamma-glutamyl carboxylase, which activates vitamin K-dependent proteins (VKDPs) through a process called carboxylation. Two particularly important VKDPs are osteocalcin in bone tissue and matrix Gla protein (MGP) in vascular tissue. Osteocalcin binds calcium to the bone matrix, promoting bone mineralisation, whilst MGP inhibits calcium deposition in arterial walls.

Without adequate vitamin K, these proteins remain undercarboxylated and cannot perform their calcium-regulating functions effectively. This may result in a situation where calcium is insufficiently deposited in bones (potentially affecting bone health) whilst simultaneously accumulating in soft tissues such as blood vessels. This dual role has positioned vitamin K2 as a nutrient of interest in bone health research, though its role in preventing vascular calcification in humans remains unproven in clinical outcome trials.

Health Benefits of Vitamin K2

Bone health and osteoporosis prevention represent the most extensively researched potential benefits of vitamin K2. By activating osteocalcin, vitamin K2 facilitates the incorporation of calcium into the bone matrix, potentially improving bone mineral density. Several observational studies have suggested an association between higher vitamin K2 intake and reduced fracture risk, particularly in postmenopausal women. In Japan, MK-4 has been approved as a treatment for osteoporosis at pharmacological doses (45 mg daily), though evidence from randomised controlled trials has shown mixed results. The European Food Safety Authority (EFSA) recognises that vitamin K contributes to the maintenance of normal bones. However, it is important to note that NICE guidance in the UK does not currently recommend vitamin K supplements for the prevention or treatment of osteoporosis.

Cardiovascular health is another area of considerable interest. The Rotterdam Study, a large prospective cohort study, found an association between higher dietary intake of vitamin K2 (but not K1) and reduced coronary calcification and lower cardiovascular mortality. The proposed mechanism involves activation of MGP, which inhibits calcium deposition in arterial walls. However, this observational evidence shows association only, not causation. Currently, there is insufficient evidence from randomised controlled trials to establish a causal relationship between vitamin K2 supplementation and improved cardiovascular outcomes.

Other potential benefits under investigation include roles in insulin sensitivity, cognitive function, and cancer prevention, though evidence remains preliminary and insufficient to support recommendations for these purposes.

Important safety note: Patients taking warfarin or other vitamin K antagonist anticoagulants should not start or stop vitamin K supplements without consulting their GP or anticoagulation clinic, as this can seriously affect anticoagulant control. If you experience unexplained bruising, bleeding, black stools, or severe headache while taking anticoagulants, seek urgent medical advice.

Vitamin K2 Food Sources and Dietary Intake

Vitamin K2 is found in a limited range of foods, making dietary intake more challenging compared to vitamin K1, which is abundant in green leafy vegetables. The richest natural source of vitamin K2 is natto, a traditional Japanese fermented soybean product, which contains exceptionally high levels of MK-7 (approximately 1,000 micrograms per 100g). However, natto's distinctive taste and texture make it an acquired preference, and it is not commonly consumed in the UK.

Animal-based foods provide moderate amounts of vitamin K2. These include:

• Dairy products: Hard and soft cheeses (particularly Gouda, Brie, and Edam) contain predominantly longer-chain menaquinones (MK-8, MK-9); butter and full-fat milk contain smaller amounts, with content influenced by the animals' diet

• Meat and poultry: Chicken, beef, and pork, especially organ meats such as liver

• Egg yolks: Particularly from free-range or grass-fed chickens

• Fermented foods: Sauerkraut and certain fermented cheeses contain bacterial-derived menaquinones

The vitamin K2 content in animal products depends significantly on the animals' diet, with grass-fed animals generally producing foods with higher K2 levels than grain-fed counterparts. Humans obtain vitamin K2 both from diet and from two other sources: gut microbiota produce various menaquinones, and some dietary vitamin K1 is converted to MK-4 in human tissues. The relative contribution of each source to overall vitamin K2 status remains uncertain.

Current UK dietary recommendations do not distinguish between vitamin K1 and K2. The NHS advises approximately 1 microgram of total vitamin K per kilogram of body weight daily (roughly 65–75 micrograms for adults). However, there is no official recommendation establishing specific requirements for vitamin K2 alone. Most UK diets provide adequate total vitamin K through consumption of green vegetables, though vitamin K2 intake may be suboptimal in individuals who consume limited fermented or animal-based foods.

Vitamin K2 Supplements: Dosage and Forms

Vitamin K2 supplements are available in the UK as standalone products or combined with other nutrients, particularly vitamin D3 and calcium. The two main supplemental forms are MK-4 and MK-7, which differ in their pharmacokinetic properties and typical dosing regimens.

MK-7 (menaquinone-7) is the most commonly available form in UK supplements, typically derived from fermented soybeans (natto extract) or produced synthetically. Due to its longer half-life, MK-7 accumulates in the bloodstream and maintains more stable serum levels. Typical supplemental doses range from 45 to 200 micrograms daily, with most products containing 100–180 micrograms. Research suggests that doses of 180–360 micrograms daily can improve markers of vitamin K status, such as undercarboxylated osteocalcin levels.

MK-4 (menatetrenone) has a shorter duration of action and is typically used at much higher pharmacological doses (45 mg daily) in clinical settings, particularly in Japan for osteoporosis treatment. This form is less commonly available in UK over-the-counter supplements.

Safety considerations: Vitamin K2 is generally well-tolerated with no established upper limit for toxicity. Supplements providing up to 1 mg per day are unlikely to cause harm for most people. However, individuals taking warfarin or other vitamin K antagonist anticoagulants should not take vitamin K2 supplements without medical supervision, as vitamin K can reduce anticoagulant efficacy and increase thrombotic risk. Patients on warfarin require stable, consistent vitamin K intake, and any supplementation must be discussed with their GP or anticoagulation clinic. Direct oral anticoagulants (DOACs) such as apixaban, rivaroxaban, edoxaban or dabigatran do not interact with vitamin K in the same manner.

Quality and regulation: In the UK, vitamin K2 supplements are regulated as food supplements rather than medicines, falling under Food Standards Agency and Trading Standards oversight. The Great Britain Nutrition and Health Claims Register permits limited claims that 'vitamin K contributes to the maintenance of normal bones' and 'normal blood clotting'. Consumers should select products from reputable manufacturers that adhere to Good Manufacturing Practice (GMP) standards. When considering supplementation, individuals should consult their GP or a registered dietitian, particularly if they have existing health conditions, take medications, or are pregnant or breastfeeding.

If you experience any suspected side effects from supplements, particularly interactions with medicines, you can report these to the MHRA Yellow Card scheme (yellowcard.mhra.gov.uk).

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