Vitamin K

Vitamin K is a fat-soluble vitamin with critical roles in blood coagulation, bone metabolism, and cardiovascular health. The name "vitamin K" comes from the German word "Koagulation," reflecting its discovery as an essential factor for blood clotting. The vitamin exists in two principal forms: vitamin K1 (phylloquinone) and vitamin K2 (menaquinones).

Vitamin K1 is the predominant dietary form, found primarily in green leafy vegetables. It is rapidly absorbed but has relatively short half-life in the body. Vitamin K2 comprises a family of compounds called menaquinones (designated MK-4 through MK-13) with different chain lengths. MK-4 is found in animal products and can be synthesized from K1, while MK-7 is produced by bacterial fermentation and found in natto and some cheeses.

The fundamental biochemical function of vitamin K is as a cofactor for the enzyme gamma-glutamyl carboxylase. This enzyme catalyzes the post-translational modification of specific proteins by adding carboxyl groups to glutamic acid residues, converting them to gamma-carboxyglutamic acid (Gla). This modification is essential for the calcium-binding ability of these proteins.

Vitamin K-dependent proteins include clotting factors II (prothrombin), VII, IX, and X, which are essential for blood coagulation. Beyond clotting, vitamin K activates osteocalcin (a bone matrix protein) and matrix Gla protein (MGP), which inhibits soft tissue calcification. This dual role makes vitamin K crucial for both bone health and cardiovascular protection.

Newborns are particularly vulnerable to vitamin K deficiency because the vitamin does not cross the placenta efficiently, breast milk contains low amounts, and the newborn gut lacks bacteria that produce vitamin K2. This is why vitamin K injection at birth is standard practice in most countries to prevent vitamin K deficiency bleeding (VKDB), a potentially life-threatening condition.

The interaction between vitamin K and anticoagulant medications (particularly warfarin) is clinically significant. Warfarin inhibits vitamin K epoxide reductase, preventing the recycling of vitamin K and reducing clotting factor synthesis. Patients on warfarin must maintain consistent vitamin K intake to ensure stable anticoagulation.

Vitamin K functions as an essential cofactor (coenzyme) for the enzyme gamma-glutamyl carboxylase. This enzyme catalyzes the post-translational carboxylation of specific glutamic acid residues in vitamin K-dependent proteins, converting them to gamma-carboxyglutamic acid (Gla) residues. This modification is absolutely required for these proteins to bind calcium ions and become biologically active.

In the liver, vitamin K-dependent clotting factors (prothrombin/factor II, factor VII, factor IX, factor X, protein C, protein S, and protein Z) require carboxylation for their function in the coagulation cascade. Without adequate vitamin K, these proteins remain in their inactive, uncarboxylated forms, leading to impaired blood clotting and bleeding tendency.

In bone, vitamin K activates osteocalcin, the most abundant non-collagenous protein in bone matrix. Carboxylated osteocalcin binds calcium with high affinity and helps anchor calcium hydroxyapatite crystals to the collagen matrix. Uncarboxylated osteocalcin cannot bind calcium effectively, potentially compromising bone mineralization. Vitamin K also activates matrix Gla protein (MGP) in cartilage and vascular smooth muscle.

The vitamin K cycle is a sophisticated recycling system that allows small amounts of vitamin K to carboxylate many protein molecules. After participating in carboxylation, vitamin K epoxide is reduced back to active vitamin K by the enzyme vitamin K epoxide reductase (VKORC1). This enzyme is the molecular target of warfarin and related anticoagulants. By inhibiting VKORC1, warfarin depletes functional vitamin K, reducing clotting factor synthesis.

Vitamin K2 (particularly MK-7) has longer half-life than K1 and may provide more sustained serum levels. MK-7 is also transported by lipoproteins differently than K1, potentially delivering vitamin K to extrahepatic tissues (bone, blood vessels) more effectively. However, the liver preferentially accumulates vitamin K for clotting factor synthesis, which may limit availability to other tissues when intake is low.

Absorption of vitamin K requires dietary fat and intact bile and pancreatic function. It is absorbed in the small intestine via chylomicrons, enters the lymphatic system, and is transported in blood associated with lipoproteins. Vitamin K is stored in the liver and other tissues, but stores are relatively small compared to other fat-soluble vitamins. The body can recycle vitamin K through the vitamin K epoxide cycle, but this capacity is limited.

Vitamin K1 is abundant in green leafy vegetables, where it functions in photosynthesis. Vitamin K2 (menaquinones) is produced by bacterial fermentation and found in fermented foods, certain cheeses, and animal products. Gut bacteria also produce some K2, though the amount absorbed is uncertain.

Vitamin K deficiency primarily causes bleeding tendency due to impaired blood clotting. It is rare in adults with normal diets but can occur with fat malabsorption, certain medications, or liver disease. Newborns are at high risk for VKDB, which can be life-threatening.

Vitamin K requirements are based on the amount needed to maintain normal blood clotting. No UL has been established because no adverse effects have been reported from high intakes of vitamin K1 or K2 from food or supplements in humans, except for individuals on anticoagulant medications.

Vitamin K supplements come as K1 (phylloquinone), K2 MK-4, or K2 MK-7. K1 is most common in supplements and effectively supports blood clotting. K2 forms, particularly MK-7, have longer half-life and may better support bone and cardiovascular health.