Vitamin K

 Vitamin K, osteoporosis and degenerative diseases of ageing.
Vermeer C, Theuwissen E.
Menopause Int. 2011 Mar;17(1):19-23.

 The function of vitamin K is to serve as a co-factor during the post-translational carboxylation of glutamate (Glu) residues into γ-carboxyglutamate (Gla) residues. The vital importance of the Gla-proteins essential for normal haemostasis is well recognized. During recent years, new Gla-containing proteins have been discovered and the vitamin K-dependent carboxylation is also essential for their function. It seems, however, that our dietary vitamin K intake is too low to support the carboxylation of at least some of these Gla-proteins. According to the triage theory, long-term vitamin K inadequacy is an independent, but modifiable risk factor for the development of degenerative diseases of ageing including osteoporosis and atherosclerosis.
PMID: 21427421

  Vitamin K2: a novel therapy for osteoporosis.
Prabhoo R, Prabhoo TR.
J Indian Med Assoc. 2010 Apr;108(4):253-4, 256-8.

 Development and maintenance of skeletal health is essential since the resultant effect of poor bone health is an increased risk of osteoporotic fracture. Osteoporosis is currently a major public health problem and with predicted demographic changes, its future health and economic impact is likely to be phenomenal. Adult bone health is predominantly governed by two factors: (i) Maximum attainment of peak bone mass; and (ii) rate of bone loss which occurs with ageing. Both aspects are determined by a combination of endogenous and exogenous factors and, although genetic influences are believed to account for up to three-quarters of the variation in bone mass, there is still room for the modifiable factors (including nutrition) to play an important role. This article covers clinical evidences of the positive effect of vitamin K2 on osteoporosis. The activity of vitamin K2 involves both an increase in the bone-building process and decrease in the bone-loss process. Article covers effect of vitamin K2 on bone homeostasis and its safety in children, hepatic and renal impairment. Vitamin K2 should be considered for prevention and treatment in those conditions known to contribute to osteoporosis. PMID: 21114195

  Dietary vitamin K2 supplement improves bone status after lung and heart transplantation.
Forli L, Bollerslev J, Simonsen S, Isaksen GA, Kvamsdal KE, Godang K, Gadeholt G, Pripp AH, Bjortuft O.
Transplantation. 2010 Feb 27;89(4):458-64.

 Osteoporosis is a problem after transplantation. Studies since the last year indicate that vitamin K plays a role in optimal bone health. The aim of this randomized, double blind, prospective longitudinal study was to investigate the effect of a dietary supplement with vitamin K2 (180 microg menakinon-7) on bone mass, the first year after lung and heart transplantation. After preoperative baseline investigation of bone mass and bone-related biochemistry, 35 lung and 59 heart recipients were postoperatively randomized to vitamin K2 or placebo and reinvestigated the following year. In all recipients, 1 year after solid organ transplantation, the difference between vitamin K2 and placebo for the lumbar spine (L2-L4) bone mineral density (BMD) was 0.028 (SE 0.014) g/cm(2), P=0.055 and for L2 to L4 bone mineral content was 1.33 (SE 1.91) g/cm(2) (P=0.5). In lung recipients separately, the difference for bone mineral content was 3.39 g (SE 1.65), P=0.048 and in heart recipients 0.45 (SE 0.02) g, P=0.9 after controlling for baseline measures. In a forward stepwise linear regression analysis fitted to model differences in the L2 to L4 BMD, controlled for possible confounding variables (including use of bisphosphonate), and the only significant predictors were organ (B=-0.065 g/cm(2), P<0.001) and vitamin K2 (B=0.034 g/cm(2), P=0.019). Insufficient vitamin D status was common, and the parathyroid hormone was highest in the K2 group indicating a higher need for vitamin D. One year of vitamin K2 supplement suggest a favorable effect on lumbar spine BMD with different response in lung and heart recipients. Vitamin D status should receive more attention. PMID: 20177349

  Studies on action of menaquinone-7 in regulation of bone metabolism and its preventive role of osteoporosis.
Tsukamoto Y.
Biofactors. 2004;22(1-4):5-19.

 The effect of menaquinone-7 (MK-7) on bone components and bone resorbing factors induced-bone resorption using the femoral-diaphyseal and – metaphyseal tissues obtained from elderly female rats in vitro were examined. Calcium content, alkaline phosphatase activity and deoxyribonucleic acid (DNA) in the diaphyseal and metaphyseal tissues in elderly females rats were significantly decreased as compared with that of young rats, indicating that aging causes a deterioration of boneformation. The presence of MK-7 (10(-6)-10(-5) M) caused a significant prevention of reduction of biochemical components. On the other hand, the bone-resorbing factor, parathyroid hormone (1-34) (PTH; 10(-7) M) and prostaglandin E(2) (PGE(2); 10(-5) M) caused a significant decrease in calcium content in the diaphyseal and metaphyseal tissues. This decreases was completely inhibited in the presence of MK-7 (10(-7)-10(-5) M). In addition, MK-7 (10(-7)-10(-5) M) completely prevented the PTH (10(-7) M) or PGE(2) (10(-5) M) induced increases in medium glucose consumption and lactic acid production by bone tissues, Furthermore, the effect of the prolonged intake of dietary MK-7 on bone loss in ovariectomized rats was investigated. As a result, it was found that the intake of experimental diets containing the fermented soybean (natto) with supplemental MK-7 caused significant elevations of MK-7 and gamma-carboxylated osteocalcin concentration, a bio marker of boneformation, in the serum of both ovariectomized rats and normal subjects, suggesting that MK-7 may play an important role in the prevention of age-related bone loss. PMID: 15630245

  Vitamin K status of healthy Japanese women: age-related vitamin K requirement for gamma-carboxylation of osteocalcin.
Tsugawa N, Shiraki M, Suhara Y, Kamao M, Tanaka K, Okano T.
Am J Clin Nutr. 2006 Feb;83(2):380-6.

 Vitamin K deficiency is associated with low bone mineral density and increased risk of bone fracture. Phylloquinone (K1) and menaquinone 4 (MK-4) and 7 (MK-7) are generally observed in human plasma; however, data are limited on their circulating concentrations and their associations with bone metabolism or with gamma-carboxylation of the osteocalcin molecule. The objectives were to measure the circulating concentrations of K1, MK-4, and MK-7 in women and to ascertain whether each form of vitamin K is significantly associated with bone metabolism. Plasma concentrations of K1, MK-4, MK-7, undercarboxylated osteocalcin (ucOC; measured by using the new electrochemiluminescence immunoassay), intact osteocalcin (iOC), calcium, and phosphorus; bone-derived alkaline phosphatase activity; and concentrations of urinary creatinine, N-terminal telopeptide, and deoxypyridinoline were measured in healthy women (n = 396). On average, MK-7 and MK-4 were the highest and lowest, respectively, of the 3 vitamers in all age groups. K1 and MK-7 correlated inversely with ucOC, but associations between nutritional basal concentration of MK-4 and ucOC were not observed. Multiple regression analysis indicated that not only K1 and MK-7 concentrations but also age were independently correlated with ucOC concentration and the ratio of ucOC to iOC. The plasma K1 or MK-7 concentration required to minimize the ucOC concentration was highest in the group aged > or =70 y, and it decreased progressively for each of the younger age groups. The definite role of ucOC remains unclear. However, if submaximal gamma-carboxylation is related to the prevention of fracture or bone mineral loss, circulating vitamin K concentrations in elderly people should be kept higher than those in young people. PMID: 16469998

  Inhibitory effect of menaquinone-7 (vitamin K2) on the bone-resorbing factors-induced bone resorption in elderly female rat femoral tissues in vitro.
Yamaguchi M, Uchiyama S, Tsukamoto Y.
Mol Cell Biochem. 2003 Mar;245(1-2):115-20.

 The inhibitory effect of menaquinone-7 (MK-7; vitamin K2) on osteoclast-like cell formation and osteoclastic bone resorption in vitro is found (Mol Cell Biochem 228: 39-47, 2001). This study, furthermore, was undertaken to determine the effect of MK-7 on the bone-resorbing factor-induced bone resorption using the femoral-diaphyseal and -metaphyseal tissues obtained from elderly female rats in vitro. Femoral-diaphyseal and -metaphyseal tissues were cultured for 48 h in Dulbecco’s modified Eagle’s medium (high glucose, 4.5%) supplemented with antibiotics and bovine serum albumin. The experimental cultures contained MK-7 (10(-7)-10(-5) M). The bone-resorbing factors, parathyroid hormone (1-34) (PTH; 10(-7) M) and prostaglandin E2 (PGE2; 10(-5) M), caused a significant decrease in calcium content in the diaphyseal and metaphyseal tissues. The PTH or PGE2-induced decrease in bone calcium content was completely inhibited in the presence of MK-7 (10(-7)-10(-5) M). In addition, MK-7 (10(-7)-10(-5) M) completely prevented the PTH (10(-7) M)- or PGE2 (10(-5) M)-induced increase in medium glucose consumption and lactic acid production by bone tissues. These results support the view that MK-7 has a direct inhibitory effect on the bone-resorbing factor-induced bone resorption in bone culture using female aged femoral tissues in vitro. PMID: 12708750