Vitamin K

Vitamin K was discovered in 1935 by Danish biochemist Henrik Dam, who observed that chicks fed a fat-free diet developed hemorrhages. Dam named the factor "Koagulationsvitamin" (coagulation vitamin), leading to the letter K. Edward Doisy later isolated and characterized phylloquinone (K1) and menadione (K3), earning the 1943 Nobel Prize in Physiology or Medicine jointly with Dam.¹

Chemically, vitamin K compounds share a 2-methyl-1,4-naphthoquinone ring. Phylloquinone (K1) has a phytyl side chain and is found in green leafy vegetables. Menaquinones (K2) have varying isoprenoid side chains (MK-4 to MK-13) and are produced by bacteria. Menadione (K3) is a synthetic provitamin that is alkylated in the liver to form MK-4.²

Vitamin K serves as a cofactor for gamma-glutamyl carboxylase, an enzyme that converts glutamic acid residues to gamma-carboxyglutamic acid (Gla) in specific proteins. These Gla proteins include clotting factors II, VII, IX, and X, as well as proteins C and S, which are essential for hemostasis. Without vitamin K, these factors are inactive, leading to prolonged clotting times and bleeding risk.³

Beyond coagulation, vitamin K-dependent proteins regulate bone metabolism. Osteocalcin, produced by osteoblasts, requires carboxylation to bind hydroxyapatite and maintain bone mineral density. Matrix Gla protein inhibits vascular calcification, suggesting a role in cardiovascular health. Epidemiological studies link higher vitamin K intake with reduced fracture risk and lower coronary artery calcification.⁴

Phylloquinone is abundant in green leafy vegetables such as kale, spinach, and broccoli, as well as in some plant oils. Menaquinones are found in fermented foods like natto (a Japanese soybean dish) and in animal products such as liver and egg yolk. Gut bacteria synthesize menaquinones, but their contribution to human vitamin K status is debated; some estimates suggest up to 50% of requirements.

The US National Academies set adequate intake (AI) at 90 µg/day for adult women and 120 µg/day for adult men. Most Western diets meet these levels, but subclinical deficiency may occur in elderly populations or those with malabsorption. Vitamin K is fat-soluble, so absorption requires dietary fat and bile salts. Deficiency is treated with oral or parenteral phylloquinone.⁵

Vitamin K antagonists, such as warfarin, are widely used anticoagulants that inhibit vitamin K epoxide reductase, depleting active vitamin K. Patients on warfarin must maintain consistent vitamin K intake to avoid fluctuations in INR. Conversely, vitamin K is the antidote for warfarin overdose and is administered to newborns prophylactically to prevent vitamin K deficiency bleeding (VKDB), a rare but serious condition.⁶

High doses of vitamin K can interfere with anticoagulant therapy, but no upper limit has been established due to low toxicity. However, menadione (K3) is no longer used clinically because it can cause hemolytic anemia in glucose-6-phosphate dehydrogenase deficiency. Research is exploring vitamin K2 supplementation for osteoporosis and vascular health, though evidence remains inconclusive.⁷

Vitamin K plays a role in sphingolipid metabolism in the brain, where it activates enzymes involved in myelin synthesis. Some studies suggest a link between vitamin K and cognitive decline, but data are preliminary.⁴

Certain antibiotics, such as cephalosporins, can impair vitamin K recycling, leading to deficiency in prolonged use. Also, vitamin K is used as a rodenticide in high doses, causing fatal hemorrhage in pests. In agriculture, vitamin K is added to animal feed to prevent deficiency in poultry and swine.

Historically, vitamin K was used to treat hemorrhagic disease of the newborn before routine prophylaxis was adopted. The discovery of vitamin K-dependent proteins beyond coagulation, such as Gas6, has opened research into cell survival and inflammation.²

Phylloquinone

Vitamin K1, found in plants, with a phytyl side chain.

Menaquinone

Vitamin K2, produced by bacteria, with isoprenoid side chains.

Menadione

Vitamin K3, a synthetic provitamin.

Gamma-glutamyl carboxylase

Enzyme that carboxylates glutamic acid residues in vitamin K-dependent proteins.

Osteocalcin

Bone protein requiring vitamin K for carboxylation.

Matrix Gla protein

Protein that inhibits vascular calcification.

Warfarin

Anticoagulant that inhibits vitamin K epoxide reductase.

Vitamin K deficiency bleeding

Hemorrhagic condition in newborns due to vitamin K deficiency.