Also see:
Intestinal Serotonin and Bone Loss
Carbohydrates and Bone Health
Parmigiano Reggiano cheese and bone health
Calcium Paradox
J Med Assoc Thai. 2009 Sep;92 Suppl5:S1-3.
The role of vitamin K2 on osteoblastic functions by using stem cell model.
Bunyaratavej N, Sila-Asna M, Bunyaratavej A.
Vitamin K2 (MK4) functions were investigated by using the induced skin cell into osteoblast compared with the control media.The real time PCR measured gene expression in both cultures at the fourth, seventh, fourteenth, twenty first, twenty eighth, thirty fifth and forty second days of culture. The gene expressions of osteocalcin, osteonectin, osteopontin, bone sialoprotein, CBFA1, Interleukin-6, Estrogen receptors and collagen type) were monitored by real time PCR. MK4 had strong power to stimulate gene expression of osteocalcin and osteonectin after one week of culture but MK4 showed weak action on gene of osteopontin, bone sialoprotein and interleukin-6. The gene of estrogens showed the marked expression of estrogen receptor beta at the fourteenth day of culture while estrogen receptor alpha did not respond. MK4 could stimulate genes of RANKL and collagen type 1. This study supported the action of vitamin K2 for enhancing the bone matrix.
Nutrition. 2001 Oct;17(10):880-7.
Vitamin K and bone health.
Weber P.
In the past decade it has become evident that vitamin K has a significant role to play in human health that is beyond its well-established function in blood clotting. There is a consistent line of evidence in human epidemiologic and intervention studies that clearly demonstrates that vitamin K can improve bone health. The human intervention studies have demonstrated that vitamin K can not only increase bone mineral density in osteoporotic people but also actually reduce fracture rates. Further, there is evidence in human intervention studies that vitamins K and D, a classic in bone metabolism, works synergistically on bone density. Most of these studies employed vitamin K(2) at rather high doses, a fact that has been criticized as a shortcoming of these studies. However, there is emerging evidence in human intervention studies that vitamin K(1) at a much lower dose may also benefit bone health, in particular when coadministered with vitamin D. Several mechanisms are suggested by which vitamin K can modulate bone metabolism. Besides the gamma-carboxylation of osteocalcin, a protein believed to be involved in bone mineralization, there is increasing evidence that vitamin K also positively affects calcium balance, a key mineral in bone metabolism. The Institute of Medicine recently has increased the dietary reference intakes of vitamin K to 90 microg/d for females and 120 microg/d for males, which is an increase of approximately 50% from previous recommendations.
Clin Calcium. 2007 Nov;17(11):1752-60.
[Experience of vitamin K2 in Thailand].
[Article in Japanese]
Bunyaratavej N.
Vitamin K(2) has dual actions, stimulates osteoblastic functions, for synthesis of osteocalcin, osteonectin and other matrix bone proteins, in addition, new finding, in stem cell culture found osteoblast producing gene expression of collagen type 1, the other action, vitamin K(2) contains mild antiresorpion by inducing the osteoclastic apoptosis. Our study found that postmenopausal and elderly women have high risk of vitamin K(2) deficiency, comparing to the normal value of young, reproductive females. The efficacy of vitamin K(2) will be fulfill benefit after 6 months of administration, prolong use will enhance of bone quality that prevent fracture.
Clin Calcium. 2008 Oct;18(10):1476-82.
[Vitamin K2].
[Article in Japanese]
Ishida Y.
Vitamin K2 has been approved for the treatment of osteoporosis in Japan since 1995. Vitamin K2 treatment in osteoporosis has been shown to inhibit the occurrence of new bone fractures and to maintain BMD. The uniqueness of the prevention of bone fractures by vitamin K2 is that there has been no direct evidence of the relationship between increase of BMD and a decrease in the occurrence of bone fractures. A recent systematic review of seven Japanese randomized controlled trials by Cockayne has also shown that supplementation with phytonadione (Vitamin K1) and menaquinone (Vitamin K2) , particularly menaquinone-4, is associated with increased BMD and reduced fracture incidence. To confirm these results, a larger well design RCT using fractures as the primary endpoint is clearly needed.
Am J Clin Nutr January 1999 vol. 69 no. 1 74-79
Vitamin K intake and hip fractures in women: a prospective study
Diane Feskanich, Peter Weber, Walter C Willett, Helaine Rockett, Sarah L Booth and Graham A Colditz
Background: Vitamin K mediates the γ-carboxylation of glutamyl residues on several bone proteins, notably osteocalcin. High serum concentrations of undercarboxylated osteocalcin and low serum concentrations of vitamin K are associated with lower bone mineral density and increased risk of hip fracture. However, data are limited on the effects of dietary vitamin K.
Objective: We investigated the hypothesis that high intakes of vitamin K are associated with a lower risk of hip fracture in women.
Design: We conducted a prospective analysis within the Nurses’ Health Study cohort. Diet was assessed in 72327 women aged 38–63 y with a food-frequency questionnaire in 1984 (baseline). During the subsequent 10 y of follow-up, 270 hip fractures resulting from low or moderate trauma were reported.
Results: Women in quintiles 2–5 of vitamin K intake had a significantly lower age-adjusted relative risk (RR: 0.70; 95% CI: 0.53, 0.93) of hip fracture than women in the lowest quintile (<109 µg/d). Risk did not decrease between quintiles 2 and 5 and risk estimates were not altered when other risk factors for osteoporosis, including calcium and vitamin D intakes, were added to the models. Risk of hip fracture was also inversely associated with lettuce consumption (RR: 0.55; 95% CI: 0.40, 0.78) for one or more servings per day compared with one or fewer servings per week), the food that contributed the most to dietary vitamin K intakes.
Conclusions: Low intakes of vitamin K may increase the risk of hip fracture in women. The data support the suggestion for a reassessment of the vitamin K requirements that are based on bone health and blood coagulation.
Clin Calcium. 2005 Apr;15(4):605-10.
[Vitamin K2 as a protector of bone health and beyond].
[Article in Japanese]
Kaneki M.
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.
Int J Gynaecol Obstet. 1997 Jan;56(1):25-30.
Serum vitamin K level and bone mineral density in post-menopausal women.
Kanai T, Takagi T, Masuhiro K, Nakamura M, Iwata M, Saji F.
OBJECTIVE:
Vitamin K is known to influence bone metabolism by facilitating the synthesis of osteocalcin (BGP). The bone mineral density decreases drastically after menopause. We investigated the relationship of bone mineral density, vitamin K levels and other biological parameters of bone metabolism in post-menopausal women.
METHODS:
Serum levels of vitamin K, BGP and other markers of bone metabolism were measured in 71 post-menopausal women (19 with reduced bone mineral density and 52 with normal bone density), and 24 women with climacteric symptoms receiving hormone replacement therapy (HRT), (6 with reduced bone mineral density and 18 with normal density).
RESULTS:
In the first group, women with reduced bone mineral density showed lower levels of vitamin K1 and K2 than those with normal bone mineral density. In the other group, the level of BGP decreased but levels of vitamin K showed no increase during HRT.
CONCLUSION:
The present findings suggested that vitamin K was related to post-menopausal bone mineral loss.
Annu Rev Nutr. 1995;15:1-22.
Role of vitamin K in bone metabolism.
Vermeer C, Jie KS, Knapen MH.
Vitamin K is a cofactor required for the formation of gamma-carboxyglutamate (Gla) residues in proteins. Osteoblasts produce at least three different Gla-containing proteins: osteocalcin, matrix Gla-protein, and protein S. After cellular secretion of these proteins, the main part of each remains bound to the hydroxyapatite matrix in bone, but their function remains unclear. Part of the newly synthesized osteocalcin is also set free into the bloodstream, where it may be used as a diagnostic marker for bone formation. Several studies have demonstrated that a poor vitamin K status is associated with an increased risk of osteoporotic bone fractures. Whether vitamin K supplementation will reduce the rate of bone loss in postmenopausal women remains a matter of debate.
J Gravit Physiol. 1998 Oct;5(2):65-9.
Bone markers during a 6-month space flight: effects of vitamin K supplementation.
Vermeer C, Wolf J, Craciun AM, Knapen MH.
Rapid bone loss is a serious health problem for astronauts during long lasting missions in space. We have recorded the changes of biochemical markers for bone metabolism in one of the astronauts during the 6-month space flight of the EUROMIR-95 mission. Immediately after launch both bone resorption markers and urinary calcium excretion increased about two fold, whereas bone formation markers remained unchanged. After 12 1/2 weeks the astronaut received vitamin K1 (10 mg/day for 6 weeks). Vitamin K is known to be involved in the formation of gamma-carboxyglutamate (Gla) in proteins, such as the calcium-binding bone Gla-proteins osteocalcin and matrix Gla-protein. Concomitant with the start of vitamin K treatment, the calcium-binding capacity of osteocalcin increased, and so did the urinary excretion of free Gla. This is suggestive for a subclinical vitamin K-deficiency in the astronaut before vitamin K-supplementation. During periods of high vitamin K status markers for bone formation (osteocalcin and bone alkaline phosphatase) had increased as compared to the first part of the flight. The mean increases were 14 and 23%, respectively. Our data suggest that increased intake of vitamin K may contribute to counteracting microgravity-induced loss of bone mass during long lasting space missions, but need confirmation in more astronauts.
Am J Clin Nutr. 2000 May;71(5):1201-8.
Dietary vitamin K intakes are associated with hip fracture but not with bone mineral density in elderly men and women.
Booth SL, Tucker KL, Chen H, Hannan MT, Gagnon DR, Cupples LA, Wilson PW, Ordovas J, Schaefer EJ, Dawson-Hughes B, Kiel DP.
BACKGROUND:
Vitamin K has been associated with bone mineral density (BMD) and risk of hip fracture. The apolipoprotein (apo) E4 allele (APOE*E4) has been associated with bone fracture through a putative effect on vitamin K transport in blood.
OBJECTIVE:
The objective was to determine the associations between vitamin K intake, apo E genotype, BMD, and hip fracture in a population-based cohort of elderly men and women.
DESIGN:
Dietary vitamin K intake was assessed with a food-frequency questionnaire in 335 men and 553 women (average age: 75.2 y) participating in the Framingham Heart Study in 1988-1989. Incidence of hip fractures was recorded from 1988 to 1995. BMD at the hip, spine, and arm was assessed on 2 separate occasions (1988-1989 and 1992-1993). Comparisons between apo E genotype and BMD were made relative to E4 allele status (at least 1 epsilon4 allele compared with no epsilon4 allele).
RESULTS:
Individuals in the highest quartile of vitamin K intake (median: 254 microg/d) had a significantly lower fully adjusted relative risk (0.35; 95% CI: 0. 13, 0.94) of hip fracture than did those in the lowest quartile of intake (median: 56 microg/d). There were no associations between vitamin K intake and BMD in either men or women. No association was found between the E4 allele and BMD, and there were no significant interactions between the E4 allele and phylloquinone intake and BMD or hip fracture.
CONCLUSIONS:
Low vitamin K intakes were associated with an increased incidence of hip fractures in this cohort of elderly men and women. Neither low vitamin K intake nor E4 allele status was associated with low BMD.
Am J Clin Nutr. 2003 Feb;77(2):512-6.
Vitamin K intake and bone mineral density in women and men.
Booth SL, Broe KE, Gagnon DR, Tucker KL, Hannan MT, McLean RR, Dawson-Hughes B, Wilson PW, Cupples LA, Kiel DP.
BACKGROUND:
Low dietary vitamin K intake has been associated with an increased risk of hip fracture in men and women. Few data exist on the association between dietary vitamin K intake and bone mineral density (BMD).
OBJECTIVE:
We studied cross-sectional associations between self-reported dietary vitamin K intake and BMD of the hip and spine in men and women aged 29-86 y.
DESIGN:
BMD was measured at the hip and spine in 1112 men and 1479 women (macro x +/- SD age: 59 +/- 9 y) who participated in the Framingham Heart Study (1996-2000). Dietary and supplemental intakes of vitamin K were assessed with the use of a food-frequency questionnaire. Additional covariates included age, body mass index, smoking status, alcohol use, physical activity score, and menopause status and current estrogen use among the women.
RESULTS:
Women in the lowest quartile of vitamin K intake (macro x: 70.2 microg/d) had significantly (P < or = 0.005) lower mean (+/- SEM) BMD at the femoral neck (0.854 +/- 0.006 g/cm(2)) and spine (1.140 +/- 0.010 g/cm(2)) than did those in the highest quartile of vitamin K intake (macro x: 309 microg/d): 0.888 +/- 0.006 and 1.190 +/- 0.010 g/cm(2), respectively. These associations remained after potential confounders were controlled for and after stratification by age or supplement use. No significant association was found between dietary vitamin K intake and BMD in men.
CONCLUSIONS:
Low dietary vitamin K intake was associated with low BMD in women, consistent with previous reports that low dietary vitamin K intake is associated with an increased risk of hip fracture. In contrast, there was no association between dietary vitamin K intake and BMD in men.
