Vitamin K

Vitamin K refers to a group of structurally related fat-soluble compounds that share a common ring able to support a specific biochemical reaction ^[2]. The main natural forms are phylloquinone, or vitamin K1, which comes chiefly from green leafy vegetables and plant oils, and the menaquinones, collectively vitamin K2, which are produced by bacteria and occur in some animal foods and fermented products such as natto ^[2]. Phylloquinone is usually the largest contributor to intake in typical diets, while the various menaquinones differ in chain length, absorption, and how long they persist in the body ^[2].

Vitamin K serves as an essential cofactor for the enzyme gamma-glutamyl carboxylase, which carries out a modification called gamma-carboxylation on a set of proteins ^[1]. This modification enables the proteins, known as vitamin K-dependent proteins, to bind calcium, which they need in order to function ^[1]. The best-known of these are several clotting factors, so vitamin K is indispensable to normal blood coagulation; other vitamin K-dependent proteins, including osteocalcin in bone and matrix Gla protein in blood vessels, link the vitamin to bone metabolism and to the regulation of tissue calcification ^[1][3].

A shortage of vitamin K impairs the production of functional clotting factors and leads to a tendency to bleed ^[2]. Newborn infants are especially vulnerable because little vitamin K crosses the placenta and their gut is not yet colonized by vitamin K-producing bacteria, so a prophylactic dose of vitamin K1 shortly after birth is standard practice to prevent a serious bleeding disorder of the newborn ^[2]. In adults, deficiency is uncommon but can arise from fat malabsorption, liver disease, or treatment with vitamin K antagonist drugs ^[1][2].

Vitamin K was discovered by the Danish scientist Henrik Dam around 1929 during studies of cholesterol, when he observed a bleeding tendency that a fat-soluble dietary factor could correct; he named it the coagulation vitamin and later shared a Nobel Prize for the work ^[2]. The anticoagulant warfarin and related drugs act precisely on this system, blocking the enzyme that recycles vitamin K to its active form, which reduces clotting factor production; people taking warfarin are therefore advised to keep their vitamin K intake steady, and vitamin K can be used as an antidote to reverse excessive anticoagulation or poisoning by warfarin-type rodenticides ^[1][2].

Vitamin K is regulated as a food and dietary supplement and is used medically to correct deficiency and for newborn prophylaxis, while a synthetic form, menadione, is restricted from human supplements in some countries because of toxicity but is permitted in animal feed ^[2]. Recommended intakes for adults have been set mainly around the needs of coagulation, and no upper limit has been established because high intakes of the natural forms have not been linked to harm ^[2]. Research continues into whether higher vitamin K intake, particularly of the menaquinone forms, benefits bone strength and vascular health, but randomized trials have so far given mixed results ^[2][3].

Vitamin K is generally safe with no established toxicity from food or typical supplements. The major caution is that it directly counteracts warfarin and similar anticoagulants, so anyone on those drugs must keep intake consistent and coordinate with their doctor. Otherwise side effects are minimal.

Vitamin K's defining interaction is with warfarin and the other coumarin anticoagulants, and it runs in both directions. Warfarin works by blocking vitamin K epoxide reductase, so vitamin K intake directly opposes it. A sudden rise in dietary or supplemental vitamin K lowers INR; a sudden fall raises it. Steadiness of intake, rather than avoidance, is what keeps anticoagulation predictable, and pharmacologic vitamin K is used deliberately to reverse over-anticoagulation.

Anything that impairs fat absorption lowers vitamin K status: orlistat, cholestyramine and colestipol, mineral oil, and the malabsorption of cholestatic liver disease. Prolonged broad-spectrum antibiotics reduce menaquinone production by gut bacteria, and cephalosporins carrying an N-methylthiotetrazole side chain, such as cefotetan and cefoperazone, inhibit vitamin K epoxide reductase themselves and have caused hypoprothrombinemia and bleeding.

Vitamin K has no effect on heparin, nor on the direct oral anticoagulants apixaban, rivaroxaban and dabigatran, none of which depend on vitamin K-dependent factor synthesis.

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