menaquinone-6 and Arteriosclerosis

Several lives of evidence indicate a protective effect of vitamin K against osteoporosis. Epidemiological studies showed that low vitamin K intake is associated with the increased risk of osteoporosis. Vitamin K2 (menatetrenone, MK-4) has been clinically used in the treatment of patients with osteoporosis in Japan, Korea and Thailand. Previous studies demonstrated the efficacy of vitamin K2 (45 mg/day) to prevent bone loss and reduce the rate of vertebral fractures, although a large, randomized intervention study is anticipated to provide more detailed evidence. Recently, vitamin K2 has been shown to reduce the progression of hepatocarcinoma. Moreover, it has been proposed that vitamin K may also have beneficial effects to prevent atherogenesis. The clarification of molecular mechanisms by which vitamin K2 exerts these salutary effects deserve further investigations.

Topics: Animals; Arteriosclerosis; Carcinoma, Hepatocellular; Dementia; Evidence-Based Medicine; Humans; Liver Neoplasms; Osteoporosis; Randomized Controlled Trials as Topic; Spinal Fractures; Vitamin K 2

The role of vitamin K in the prevention and treatment of osteoporosis and arterial calcification is examined.. Vitamin K is essential for the activation of vitamin K-dependent proteins, which are involved not only in blood coagulation but in bone metabolism and the inhibition of arterial calcification. In humans, vitamin K is primarily a cofactor in the enzymatic reaction that converts glutamate residues into gamma-carboxyglutamate residues in vitamin K-dependent proteins. Numerous studies have demonstrated the importance of vitamin K in bone health. The results of recent studies have suggested that concurrent use of menaquinone and vitamin D may substantially reduce bone loss. Menaquinone was also found to have a synergistic effect when administered with hormone therapy. Several epidemiologic and intervention studies have found that vitamin K deficiency causes reductions in bone mineral density and increases the risk of fractures. Arterial calcification is an active, cell-controlled process that shares many similarities with bone metabolism. Concurrent arterial calcification and osteoporosis have been called the "calcification paradox" and occur frequently in postmenopausal women. The results of two dose-response studies have indicated that the amount of vitamin K needed for optimal gamma-carboxylation of osteocalcin is significantly higher than what is provided through diet alone and that current dosage recommendations should be increased to optimize bone mineralization. Few adverse effects have been reported from oral vitamin K.. Phytonadione and menaquinone may be effective for the prevention and treatment of osteoporosis and arterial calcification.

Topics: Antifibrinolytic Agents; Arteriosclerosis; Female; Humans; Osteoporosis, Postmenopausal; Treatment Outcome; Vitamin K; Vitamin K 1; Vitamin K 2

Vitamin K-dependent proteins, including matrix Gla-protein, have been shown to inhibit vascular calcification. Activation of these proteins via carboxylation depends on the availability of vitamin K. We examined whether dietary intake of phylloquinone (vitamin K-1) and menaquinone (vitamin K-2) were related to aortic calcification and coronary heart disease (CHD) in the population-based Rotterdam Study. The analysis included 4807 subjects with dietary data and no history of myocardial infarction at baseline (1990-1993) who were followed until January 1, 2000. The risk of incident CHD, all-cause mortality, and aortic atherosclerosis was studied in tertiles of energy-adjusted vitamin K intake after adjustment for age, gender, BMI, smoking, diabetes, education, and dietary factors. The relative risk (RR) of CHD mortality was reduced in the mid and upper tertiles of dietary menaquinone compared to the lower tertile [RR = 0.73 (95% CI: 0.45, 1.17) and 0.43 (0.24, 0.77), respectively]. Intake of menaquinone was also inversely related to all-cause mortality [RR = 0.91 (0.75, 1.09) and 0.74 (0.59, 0.92), respectively] and severe aortic calcification [odds ratio of 0.71 (0.50, 1.00) and 0.48 (0.32, 0.71), respectively]. Phylloquinone intake was not related to any of the outcomes. These findings suggest that an adequate intake of menaquinone could be important for CHD prevention.

Topics: Aortic Diseases; Arteriosclerosis; Calcinosis; Cholesterol; Cholesterol, HDL; Coronary Disease; Diet; Energy Intake; Female; Humans; Male; Middle Aged; Mortality; Myocardial Infarction; Netherlands; Odds Ratio; Prospective Studies; Risk Factors; Sex Characteristics; Vitamin K 1; Vitamin K 2

Gamma-Carboxyglutamic acid (Gla)-containing protein, synthesized in the presence of vitamin K, has been found in atherogenic plaques, but the pharmacological effect of vitamin K on atherosclerosis is unclear. We examined whether vitamin K2 (menatetrenone) could affect the progression of both atherosclerosis and hypercoagulability in hypercholesterolemic rabbits. Vitamin K2 in daily doses of 1, 10 and 100 mg/kg was given with a 0.5% cholesterol diet for 10 weeks to 8 rabbits each. The plasma levels of total-cholesterol in the vitamin K2-treated groups were clearly lower than that of the hypercholesterolemic control group. The excessive dose of vitamin K2, even at the high dose of 100 mg/kg/day for 10 weeks, did not accelerate the progression of atherosclerosis and did not promote the coagulative tendency in the rabbits. In contrast, the vitamin K2 treatment (1 to 10 mg/kg/day) suppressed the progression of atherosclerotic plaques, intima-thickening and pulmonary atherosclerosis, the increase of ester-cholesterol deposition in the aorta, and both the elevation in plasma factor X level and increase in Hepaplastin test value in the rabbits. These results indicate that the pharmacological dose of vitamin K2 prevents both the progression of atherosclerosis and the coagulative tendency by reducing the total-cholesterol, lipid peroxidation and factor X activity in plasma, and the ester-cholesterol deposition in the aorta in hypercholesterolemic rabbits.

Topics: Animals; Aorta; Arteriosclerosis; Blood Coagulation; Hemostatics; Hypercholesterolemia; Lipid Peroxides; Male; Rabbits; Vitamin K; Vitamin K 2