Vitamin K

Phylloquinone (vitamin K1)

vitamin K from plant sources, found in high quantities leafy green vegetables and moderate amounts in plant based oils (soybean, canola, rapeseed)

vitamin K found in plant oils is more bioavailable and readily absorbed

Menaquinone/Mk (vitamin K2)

found in animal sources like liver, fished, fermented goods, milk, butter, and some soybean products; can also be endogenously synthesized by intestinal bacteria

Menadione (vitamin K3)

synthetic/supplement form of vitamin K

Digestion

phylloquinone requires no digestion

absorption of vitamin K

incorporated into micelle along with bile, digested lipids, and other fat-soluble vitamins

What enhances vitamin K absorption?

dietary lipids, bile salts, lipase, and pancreatic juices

What reduces Vitamin K absorption?

fat malabsorption disorders and insufficient bile and pancreatic secretion

Transport of Vitamin K

Within enterocytes, Vitamin K is incorporated into chylomicrons and transported into the lymphatic system and then the circulatory system.

Chylomicron remnants deliver any unused Vitamin K to the liver and then VLDL transport vitamin K from the liver to the tissues again

Main circulatory form of vitamin K in the blood

phylloquinone

Where is vitamin K primarily stored?

in the cell membranes

How is vitamin K excreted?

primarily in the feces via bile, and a little bit in the urine

Vitamin K role in blood clotting and bone formation

many proteins involved in bone formation and blood clotting are vitamin K dependent and require it for carboxylation and activation

general mechanism of vitamin K

Vitamin K serves as a cofactor for Vitamin K dependent gamma glutanyl-carboxylase, which converts a glutamic acid residue to an activated Gla-protein, which can bind with calcium and reacts with cell components like phospholipids to affect bone clotting and bone mineralization

intrinsic pathway of blood clotting

internal bleeding

extrinsic factor of blood clotting

external bleeding, ex: cut to skin

Overview of blood clotting, steps 3-8

1. a series of reactions generates the inactive clotting factor X (Stuart factor)

2. Vitamin K and calcium activate clotting factors to make them active

3. Active clotting factor Xa converts prothrombin to thombrin

4. Thombrin and fibrin stabilizing factor XIIIa form fibrin, which aggregates to produce an insoluble clot and stops the bleeding

How does Warfarin stop the Vitamin K cycle?

Warfarin blocks the action of Vitamin K epoxide reductase and quinone reductase

osteocalcin

main vitamin K dependent protein in bone

following vitamin K dependent carboxylation, osteocalcin’s Gla residues facilitates binding of calcium to the hydroxyapatite lattice in bones

osteonectin

phosphoprotein that binds to calcium and collagen

AI for vitamin K

adult men: 120ug/day

adult women: 90ug/day

What is the AI for vitamin K based on?

the amount needed for coagulation function, but levels may not be optimal to maximize coagulation of proteins needed for bone health

evaluation of Vitamin K status

plasma or serum phylloquinone: reflection of recent Vitamin K intake

blood clotting or prothrombin: not very sensitive

levels of under-carboxylated Vitamin K dependent protein or ratio of under-to-fully carboxylated proteins

Vitamin K toxicity

no UL/ known toxicity established, but some side effects may occur from excess intake of synthetic menadione

Vitamin K deficiency

unlikely but can cause nosebleeds, easy bruising, and in severe cases hemorrhage

Populations at risk of Vitamin K deficiency

newborns, older adults, chronic antibiotic therapy, liver disease, fat and GI malabsorption

Which vitamins antagonize vitamin K action and inhibit Vitamin K dependent carboxylation?

vitamins A and E

Which vitamins are needed for bone formation (with Vitamin K)?

calcium and vitamin D

orlistat

a weight loss drug that reduces absorption of fat and fat soluble vitamins like Vitamin K

Coumadin

inhibits enzymes in the Vitamin K cycle, reducing blood clotting

bile acid sequestrants

reduces cholesterol levels by preventing reabsorption of bile acids but may also reduce absorption of vitamin K and other fat soluble vitamins