| Vitamin K the “coagulation vitamin“ |
| Vitamin K is short for “coagulation vitamin“ (German: Koagulationsvitamin)– named after its effect on blood coagulation. There is no one substance behind this vitamin, but instead it refers to a group of various substances with a naphthoquinone structure and antihemorrhagic activity. These include phylloquinone (vitamin K1), menaquinone (vitamin K2) and menadione (vitamin K3) (1). Vitamin K is absorbed in the proximal small intestine by active transport. As with all fat-soluble vitamins, an adequate amount of bile acid and pancreatic enzymes are required for absorption (2). |
| From blood coagulation to bone metabolism in 50 years |
| For half a century, science assumed that the only essential role of vitamin K was in the synthesis of blood coagulation factors. However, with the identification of vitamin K-dependent Gla proteins it quickly became clear that vitamin K has a much broader activity spectrum in the body than previously recognized. The various Gla proteins all contain the typical component γ-carboxyglutamate (= Gla), for which vitamin K is required to biosynthesize. Gla proteins include substances as diverse as prothrombin, which is required for blood coagulation, osteocalcin, which can bind hydroxyapatite and is thus involved in bone mineralization, Matrix-Gla protein (MGP), which prevents the calcification of arteries and tissue, or the growth factor gas-6, which plays a role in cartilage differentiation. While the Gla proteins for blood coagulation are synthesized in the liver, the newly discovered Gla proteins are formed in various tissues (3). |
| Undercarboxylation as a biomarker for vitamin K deficiency |
| The molecular function of vitamin K has now been described in detail: It acts as a cofactor for the enzyme gamma-glutamyl carboxylase (GGCX), which is located in the endoplasmic reticulum and catalyzes the conversion of the amino acid glutamine to gla. Each Gla protein contains several of these Gla structures located at defined positions. If vitamin K is lacking, undercarboxylated or non-carboxylated Gla proteins with insufficient activity are produced. These defective Gla proteins can only perform their functions to a limited extent and can lead to far-reaching disorders. They are also regarded as biomarkers for the status of vitamin K. For example, undercarboxylated osteocalcin (ucOC) is the most sensitive marker for vitamin K status and bone metabolism disorders. Vitamin K deficiency is also the explanation for the paradox of osteoporosis with associated tissue calcification. Here both the carboxylation of osteocalcin and that of the matrix gla protein is disturbed (4). |
| Vitamin K deficiency is common |
| Measures of blood coagulation parameters in health adults, i.e. of hepatic Gla proteins,, generally do not show any undercarboxylation. Based on this fact, the reference values for the daily intake of vitamin K was established at 60 – 80 μg. However, if the extrahepatic Gla proteins are tested for undercarboxylation, it is shown that in non-supplemented adults both osteocalcin and the Matrix Gla protein are present in non-carboxylated (i.e. ineffective) form at a rate of 20 – 30 %. Only with an additional supply of > 1 mg vitamin K1 or 200 μg Vitamin K2 is the osteocalcin almost completely carboxylated, so that bone metabolism is ensured. This finding increased the recommended daily intake of vitamin K to to 100 – 400 μg. |
| Vitamin K2 – an integral part of modern osteoporosis therapy |
Reduced carboxylation of osteocalcin can often be observed in osteoporosis patients (5). Studies also show a connection between low alimentary vitamin K intake, bone density and an increased risk of femoral neck fractures. The American longitudinal study Nurses' Health Study (NHS), which studied more than 72,000 women for 10 years, showed as early as 1999 that the women with the lowest vitamin K intake had a 30% higher risk of hip fracture compared to the women with the highest intake (6).
IA Japanese study conducted a meta-analysis of randomized-controlled studies with adults who supplemented with vitamin K1 or vitamin K2 for at least 6 months. Of the 13 clinical studies with data on bone loss and 7 studies on fractures, all but one showed that supplemental intake of vitamin K1 or vitamin K2 inhibits bone density loss. In particular, a relationship between vitamin K2 and bone density wasbe determined. Thus, vitamin K2 was most effective in all 7 studies. It reduced the risk of vertebral fractures by 60%, hip fractures by 77% and the risk for all non-vertebral fractures by 81% (7). Postmenopausal women in particular seem to benefit from vitamin K supplementation (8). Due to its importance for bone mineralization, adequate vitamin K intake should be ensured in osteoporosis prevention and therapy. |
| Vitamin K also relevant in osteoarthritis |
| Vitamin K also seems to play a role in osteoarthritis (9) (10). For example, Japanese researchers have shown that a low vitamin K intake is a risk factor for gonarthrosis. In 719 patients, the severity of knee joint arthrosis was radiologically determined and at the same time the nutrient intake was recorded over a period of one month. Among the nutritional factors, only vitamin K intake was associated with the prevalence of osteoarthritis (9). |
| K1 or K2? MK-4 or MK-7? |
| In a direct comparison of the two forms vitamin K1 (phylloquinone) and vitamin K2 (menaquinone-4 and menaquinone-7), vitamin K2 seems to be the more biologically active form. However, the two form of K2 differ fundamentally: menaquinone-4 (MK-4), which is used in pharmacological preparations (45 mg/d), and menaquinone-7 (MK-7), which also shows therapeutic effects in lower dosages. The resorption rate of MK-7 is 6 to 8 times higher compared to K1 and its half-life in plasma is significantly longer. |
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