Phylloquinone

Phylloquinone is one of the two main natural forms of vitamin K, a group of fat-soluble vitamins based on the chemical structure of 2-methyl-1,4-naphthoquinone; phylloquinone carries a long phytyl side chain and is designated vitamin K1 ^[4]. It is the plant-derived form and the principal source of vitamin K in most diets, whereas the other family, the menaquinones or vitamin K2, is produced largely by bacteria ^[2][4].

Phylloquinone is found in green leafy vegetables, vegetable oils, and some fruit, and it is especially concentrated in leaves because it serves a role in the plant itself, acting as an electron carrier in Photosystem I during photosynthesis ^[4]. In animals its importance is different: it is an essential cofactor for the enzyme that activates a set of proteins known as vitamin K-dependent proteins ^[1][2].

The best-known of these are the blood-clotting factors made in the liver, namely factors II (prothrombin), VII, IX, and X, along with the natural anticoagulant proteins C and S; without enough vitamin K these proteins cannot function and bleeding results ^[1]. The same activation process works on proteins outside the liver, including osteocalcin in bone and matrix Gla protein in blood vessels, giving vitamin K additional roles in bone and vascular biology ^[1][3]. Phylloquinone was first isolated in 1939, and the discovery of vitamin K earned Henrik Dam and Edward Doisy the Nobel Prize in 1943.

As a medicine, phylloquinone (phytomenadione) is used to treat and prevent bleeding caused by vitamin K deficiency, to reverse excessive anticoagulation from warfarin, and to manage bleeding tendencies in conditions such as obstructive jaundice and fat malabsorption ^[2]. A widely used application is the routine injection given to newborns to prevent vitamin K deficiency bleeding, a serious hemorrhagic condition of early infancy ^[2]. It is available in oral and injectable forms and is included on the World Health Organization's List of Essential Medicines ^[2]. Interest in vitamin K for bone health stems from its activation of osteocalcin, and while diets high in vitamin K have been linked in observational studies to fewer fractures, controlled trials of phylloquinone have not shown increases in bone mineral density, and current evidence is considered insufficient to recommend routine supplements for osteoporosis ^[3].

Vitamin K1 is very safe with no established toxicity from food or supplements. The critical caveat is that it directly opposes warfarin, so people on that blood thinner must keep intake consistent and coordinate with their doctor. Newborns are routinely given vitamin K to prevent hemorrhagic disease.

Phylloquinone, given clinically as phytonadione, has one interaction that defines it: it directly antagonizes warfarin and the other coumarin anticoagulants. Warfarin works by blocking vitamin K epoxide reductase and starving the gamma carboxylation of factors II, VII, IX and X; supplying vitamin K restores that carboxylation and the anticoagulant effect falls away. This is the basis of reversal in bleeding, and it is also why swings in dietary or supplemental vitamin K destabilize a previously steady INR. A large dose replenishes tissue stores and can leave someone resistant to warfarin for a week or more, which is a real problem when anticoagulation has to be restarted. Direct oral anticoagulants such as apixaban and rivaroxaban do not act through vitamin K and are unaffected.

Phylloquinone is fat soluble, so anything that impairs fat absorption reduces it: orlistat, bile acid sequestrants such as cholestyramine and colesevelam, and mineral oil. Prolonged broad spectrum antibiotics suppress the gut bacteria that make menaquinones, which can lower vitamin K status and exaggerate the response to an anticoagulant.

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