Importance of Vitamin K

Vitamin K is a fat-soluble vitamin. Originally identified for its role in the process of blood clot formation ("K" is derived from the German word "koagulation"), vitamin K is essential for the functioning of several proteins involved in physiological processes that encompass, but are not limited to, the regulation of blood clotting (coagulation). Naturally, occurring forms of vitamin K include a number of vitamers known as vitamin K1 and vitamin K2. Vitamin K1 or phylloquinone is synthesized by plants and is the predominant form in the diet. Vitamin K2 includes a range of vitamin K forms collectively referred to as menaquinones. Most menaquinones are synthesized by human intestinal microbiota and found in fermented foods and in animal products. Menaquinones differ in length from 1 to 14 repeats of 5-carbon units in the side chain of the molecules. These forms of vitamin K are designated menaquinone-n (MK-n), where n stands for the number of 5-carbon units (MK-2 to MK-14). Widely used in animal husbandry, the synthetic compound known as menadione (vitamin K3) is a provitamin that needs to be converted to menaquinone-4 (MK-4) to be active.

Vitamin K functions as a cofactor for the enzyme, γ-glutamylcarboxylase (GGCX), which catalyzes the carboxylation of the amino acid glutamic acid (Glu) to γ-carboxyglutamic acid (Gla). Vitamin K-dependent γ-carboxylation that occurs only on specific glutamic acid residues in identified vitamin K-dependent proteins (VKDP) is critical for their ability to bind calcium.

Although vitamin K is a fat-soluble vitamin, the body stores very small amounts that are rapidly depleted without regular dietary intake. Perhaps because of its limited ability to store vitamin K, the body recycles it through a process called the vitamin K-epoxide cycle. The vitamin K cycle allows a small amount of vitamin K to be reused many times for protein carboxylation, thus decreasing the dietary requirement. Briefly, vitamin K hydroquinone (reduced form) is oxidized to vitamin K epoxide (oxidized form). The reaction enables γ-glutamylcarboxylase to carboxylate selective glutamic acid residues on vitamin K-dependent proteins. The recycling of vitamin K epoxide (oxidized form) to hydroquinone (reduced form) is carried out by two reactions that reduce vitamin K epoxide (KO) to vitamin K quinone and then to vitamin K hydroquinone (KH2). Additionally, the enzyme vitamin K oxidoreductase (VKOR) catalyzes the reduction of KO to vitamin K quinone and may be involved — as well as another yet-to-defined reductase — in the production of KH2 from vitamin K quinone. The anticoagulant drug warfarin acts as a vitamin K antagonist by inhibiting VKOR activity, hence preventing vitamin K recycling (see Coagulation).

The ability to bind calcium ions (Ca2+) is required for the activation of the several vitamin K-dependent clotting factors, or proteins, in the coagulation (clotting) cascade. The term, coagulation cascade, refers to a series of events, each dependent on the other, that stop bleeding through clot formation. Vitamin K-dependent γ-carboxylation of specific glutamic acid residues in those proteins makes it possible for them to bind calcium. Factors II (prothrombin), VII, IX, and X make up the core of the coagulation cascade. Protein Z appears to enhance the action of thrombin (the activated form of prothrombin) by promoting its association with phospholipids in cell membranes. Protein C and protein S are anticoagulant proteins that provide control and balance in the coagulation cascade; protein Z also has an anticoagulatory function. Control mechanisms for the coagulation cascade exist since uncontrolled clotting may be as life threatening as uncontrolled bleeding. Vitamin K-dependent coagulation factors are synthesized in the liver. Consequently, severe liver disease results in lower blood levels of vitamin K-dependent clotting factors and an increased risk for uncontrolled bleeding (hemorrhage).

In January 2001, the US Food and Nutrition Board (FNB) of the Institute of Medicine established the adequate intake (AI) level for vitamin K based on consumption levels in healthy individuals (Table 1). The AI for infants was based on estimated intake of vitamin K from breast milk (42).

Table 1. Adequate Intake (AI) for Vitamin K

Life Stage	Age	Males (μg/day)	Females (μg/day)
Infants	0-6 months	2.0	2.0
Infants	7-12 months	2.5	2.5
Children	1-3 years	30	30
Children	4-8 years	55	55
Children	9-13 years	60	60
Adolescents	14-18 years	75	75
Adults	19 years and older	120	90
Pregnancy	18 years and younger	-	75
Pregnancy	19 years and older	-	90
Breast-feeding	18 years and younger	-	75
Breast-feeding	19 years and older	-	90

Phylloquinone (vitamin K1) is the major dietary form of vitamin K in most diets. Green leafy vegetables and some plant oils (soybean, canola, olive, and cottonseed) are major contributors of dietary vitamin K. However, phylloquinone bioavailability from green vegetables is lower than in oil and supplements. Also, the phylloquinone content of green vegetables depends on their content in chlorophyll (green pigment), so that outer leaves have more phylloquinone than inner leaves. The efficiency of phylloquinone intestinal absorption varies among plant sources and is increased with the addition of a fat source to a meal. Finally, the hydrogenation of vegetable oils may decrease the absorption and biological effect of dietary phylloquinone. If you wish to check foods for their nutrient content, including phylloquinone, search the USDA food composition database. A number of phylloquinone-rich foods are listed in Table 2, with their content in phylloquinone expressed in micrograms (μg).

Table 2. Some Food Sources of Phylloquinone

Food	Serving	Phylloquinone (μg)
Kale, raw	1 cup (chopped)	472
Swiss chard, raw	1 cup	299
Parsley, raw	¼ cup	246
Broccoli, cooked	1 cup (chopped)	220
Spinach, raw	1 cup	145
Watercress, raw	1 cup (chopped)	85
Leaf lettuce (green), raw	1 cup (shredded)	46
Soybean oil	1 Tablespoon	25
Canola oil	1 Tablespoon	10
Olive oil	1 Tablespoon	8
Cottonseed oil	1 Tablespoon	3