Tag Archives: positive

Low Vitamin K1, but Not K2, Associated with Hip Fracture

Abstract

Intake of vitamin K1 and K2 and risk of hip fractures: The Hordaland Health Study.

Evidence of the effect of vitamin K on bone health is conflicting. The aim was to investigate the association between intake of vitamins K1 and K2 and subsequent risk of hip fracture in a general population sample, as well as potential effect modification by apolipoprotein E gene (APOE) status by presence of the E4 allele.
1238 men and 1569 women 71-75 years of age were included in the community-based Hordaland Health Study 1997-1999 in Western Norway. Information on hip fracture was obtained from hospitalizations in the region from enrolment until 31 December 2009. Information on intake of vitamins K1 and K2 collected at baseline was used as potential predictors of hip fracture in Cox proportional hazards regression analyses.
Participants in the lowest compared to the highest quartile of vitamin K1 intake had increased risk of suffering a hip fracture (hazard ratio (HR)=1.57 [95% CI 1.09, 2.26]). Vitamin K2 intake was not associated with hip fracture. Presence of APOE4-allele did not increase the risk of hip fracture, nor was there any effect modification with vitamin K1 in relation to risk of hip fracture.
A low intake of vitamin K1, but not K2, was associated with an increased risk of hip fractures.

Apalset EM, Gjesdal CG, Eide GE, Tell GS
Bone Nov 2011
PMID: 21839190

Review: Vitamin K and Bone Health 1998-2008

Abstract

Update on the role of vitamin K in skeletal health.

A protective role for vitamin K in bone health has been suggested based on its role as an enzymatic cofactor. In observational studies, vitamin K insufficiency is generally associated with lower bone mass and increased hip fracture risk. However, these findings are not supported in randomized controlled trials (RCT) of phylloquinone (vitamin K(1)) supplementation and bone loss at the hip in the elderly. This suggests that increased vegetable and legume intakes may simultaneously improve measures of vitamin K status and skeletal health, even though the mechanisms underlying these improvements may be independent of each other. Menaquinone-4 (vitamin K(2)), when given at pharmacological doses, appears to protect against fracture risk and bone loss at the spine. However, there are emerging data that suggest the efficacy of vitamin K supplementation on bone loss is inconclusive.

Shea MK, Booth SL
Nutr. Rev. Oct 2008
PMID: 18826451 | Free Full Text

This is a great review of the different forms of Vitamin K and their benefits for bone. The full study includes a table listing many studies dated from 1998 to 2008 with their outcomes. I highly recommend reading the full text.

MK-4 in doses of 45 mg/d is used as a pharmacological treatment for osteoporosis in Japan, so there are numerous randomized control studies that have assessed the efficacy of MK-4 supplementation on skeletal health. Such doses cannot be attained from the diet, regardless of the form of vitamin K consumed. Phylloquinone from the diet is converted to MK-4 in certain tissues, including bone, but the proportion of phylloquinone that is converted is not known and no dose-dependent data are available for this conversion.

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As reviewed in an earlier volume of this journal,60 studies indicate a therapeutic dose (45 mg/day) of MK-4 has a beneficial effect on spine or metacarpal BMD and fracture61–76 (Table 2). There is also improvement in bone turnover, as measured by circulating markers of bone formation and bone resorption, in response to MK-4 supplementation studies.71,72,76,77 In a separate systematic review and analysis of randomized clinical trials assessing the influence of vitamin K supplementation on hip fracture, Cockayne et al.78 concluded that supplementation with MK-4 for longer than 6 months reduces risk for hip and vertebral fracture. Included in that analysis were 12 studies that used daily doses of 45 mg/d of MK-4. As discussed by the authors, several of the studies used for the meta-analysis lacked sufficient sample size,64–66,70,73,79 were non-placebo-controlled intervention trials,70–74,76,77,80 and/or used concurrent treatment with calcium and/or vitamin D.62,69,75,76

It was subsequently disclosed that a large unpublished surveillance study conducted in Japan (n > 3000) did not find a protective effect of MK-4 supplementation (45 mg/day) on bone loss and fracture in the elderly, and that inclusion of this study may have altered the results of the meta-analysis.81 More recently, two placebo-controlled studies with large sample sizes reported no protective effect of 45 mg/d of MK-4 on hip BMD.59,67 Prior to these two publications, the majority of MK-4 supplementation studies did not report hip BMD as an outcome (Table 2). Given the heterogeneous quality of the studies used and considering the null findings of more recent, larger, placebo-controlled trials and unpublished surveillance data, prior systematic reviews and meta-analyses may need to be revisited.

 

Review: Vitamin K May Reduce Fractures

Abstract

Vitamin K and bone health.

Vitamin K has been purported to play an important role in bone health. It is required for the gamma-carboxylation of osteocalcin (the most abundant noncollagenous protein in bone), making osteocalcin functional. There are 2 main forms (vitamin K1 and vitamin K2), and they come from different sources and have different biological activities. Epidemiologic studies suggest a diet high in vitamin K is associated with a lower risk of hip fractures in aging men and women. However, randomized controlled trials of vitamin K1 or K2 supplementation in white populations did not increase bone mineral density at major skeletal sites. Supplementation with vitamin K1 and K2 may reduce the risk of fractures, but the trials that examined fractures as an outcome have methodological limitations. Large well-designed trials are needed to compare the efficacies of vitamin K1 and K2 on fractures. We conclude that currently there is not enough evidence to recommend the routine use of vitamin K supplements for the prevention of osteoporosis and fractures in postmenopausal women.

Hamidi MS, Gajic-Veljanoski O, Cheung AM
J Clin Densitom. 2013 Oct-Dec
PMID: 24090644

Vitamin K1 and K2 Reversed Bone Loss in Obese Mice

Abstract

Vitamin K1 (phylloquinone) and K2 (menaquinone-4) supplementation improves bone formation in a high-fat diet-induced obese mice.

Several reports suggest that obesity is a risk factor for osteoporosis. Vitamin K plays an important role in improving bone metabolism. This study examined the effects of vitamin K1 and vitamin K2 supplementation on the biochemical markers of bone turnover and morphological microstructure of the bones by using an obese mouse model. Four-week-old C57BL/6J male mice were fed a 10% fat normal diet group or a 45% kcal high-fat diet group, with or without 200 mg/1000 g vitamin K1 (Normal diet + K1, high-fat diet + K1) and 200 mg/1000 g vitamin K2 (Normal diet + K2, high-fat diet + K2) for 12 weeks. Serum levels of osteocalcin were higher in the high-fat diet + K2 group than in the high-fat diet group. Serum OPG level of the high-fat diet group, high-fat diet + K1 group, and high-fat diet + K2 group was 2.31 ± 0.31 ng/ml, 2.35 ± 0.12 ng/ml, and 2.90 ± 0.11 ng/ml, respectively. Serum level of RANKL in the high-fat diet group was significantly higher than that in the high-fat diet + K1 group and high-fat diet + K2 group (p<0.05). Vitamin K supplementation seems to tend to prevent bone loss in high-fat diet induced obese state. These findings suggest that vitamin K supplementation reversed the high fat diet induced bone deterioration by modulating osteoblast and osteoclast activities and prevent bone loss in a high-fat diet-induced obese mice.

Kim M, Na W, Sohn C
J Clin Biochem Nutr Sep 2013
PMID: 24062608 | Free Full Text

Vitamin K is related to blood coagulation, assisting the promotion of OC carboxylation of γ-glutamic acid, which is produced by osteoblasts, and aiding in bone formation by coupling carboxylated OC with phosphine.(15) Many studies have demonstrated that low intake of vitamin K decreases bone density, and that this is a factor that increases osteoporosis and bone fracture.(16) In the study by Booth et al.,(17) low intake of vitamin K1 led to low bone density, and was a factor for increased risk of bone fracture. When vitamin K1 was administered to human bone marrow culture, osteoclast formation was inhibited.(13) After administering vitamin K2 to osteoblasts, real-time gene expression analysis found that the OC, OPG, and RANKL genes were expressed, demonstrating that vitamin K2 has an influence on osteoblasts and osteoclasts.(18) In addition, vitamin K2 supplementation in patients with osteoporosis necessitated by the administration of glucocorticoids inhibited OPG decrease, and had effects of bone loss prevention.(19) Vitamin K2 supplementation in patients with rheumatoid arthritis accompanied with osteoporosis decreased RANKL levels and inhibited osteoclast activation.(20) Therefore, vitamin K affects bone condition both in healthy adults and in patients with specific diseases.

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The results of the bone density analysis revealed an increase with the vitamin K1 and K2 supplementation in high-fat diets. Studies on the relationship between bone density and vitamin K generally have used dual-energy x-ray absorptiometry or ultrasonic densitometry,(32) but this study used high-resolution 3D micro-CT to analyze the morphologic microstructure of trabecular bone. In the study by Fujikawa et al.,(24) the Tb.N increased when vitamin K2 and calcium were fed to ovariectomized mice, and the Tb.Sp decreased. Yamaguchi et al.,(33) also fed vitamin K2 to ovariectomized rats, and reported that it prevented bone loss. These two studies used osteoporosis-induced animals, and the methods differed from those in this study, in which obesity-induced mice were fed vitamin K supplements. In this study, even though there was no significantly statistical difference in the microstructure analysis between the groups, but BV, Tb.N, and Tb.Sp were seemed to be better in the vitamin K2-supplemented group than those in the HF group, indicating that vitamin K2 may play a role in protecting the structures of trabecular bone.

[…]

The effects of vitamin K1 and K2 supplementation in normal diet on bone metabolism were not statistically significant. However, vitamin K1 and K2 supplementation in a high-fat diet could prevent a decrease in bone density, and vitamin K2 had a greater effect on this parameter. Therefore, vitamin K2 increases OPG, a marker related to bone density and the metabolism of osteoclasts and osteoblasts, and it decreases RANKL, and thus has an influence on bone metabolism. This study has showed the effects of vitamin K on bone density and metabolism in animals, but further studies are needed to determine whether the same holds true for obese humans. Future studies would need to perform bone measurement and biochemical examinations on the bone microstructures and metabolism in humans.

 

Review: MK-4 Stimulates Osteoblasts

Abstract

[Effect of vitamin K on bone material properties].

Collagen cross-links are determinants of bone quality. Because vitamin K is thought to ameliorate bone quality, we summarized the literature regarding the effect of vitamin K such as menatetorenone (MK-4) on bone matrix property in the review. MK-4 seems to stimulate the osteoblastic activity. This results in the increase in collagen accumulation and lysyl oxidase controlled enzymatic cross-links in bone. Furthermore, vitamin K stimulates the secretion of collagen binding protein regulating proper fibrillogenesis such as leucine-rich repeat protein (tsukushi). This kinds of non-collagenous proteins induced by the treatment of vitamin K may also affect proper collagen cross-link formation and show the favorable effect on bone material quality.

Saito M
Clin Calcium Dec 2009
PMID: 19949271

Review: Vitamin K1 Improves Bone Strength and Reduces Fractures

Abstract

[Postmenopausal osteoporosis. Role of vitamin K in the prevention of osteoporosis].

Low vitamin K1 intake and low plasma vitamin K1 levels are associated with low bone mineral density (BMD) and increased osteoporotic fracture risk in postmenopausal women. Despite the lack of a significant change or the occurrence of only a modest increase in bone mineral density, high-dose vitamin K(1) supplementation improved indices of bone strength in the femoral neck and reduced the incidence of clinical fractures.

Malinova M
Akush Ginekol (Sofiia) 2013
PMID: 24294745

Vitamin K1 and Vitamin D are Independently and Synergistically Associated with Lower Hip Fracture in Elderly

Abstract

Vitamin K1 and 25(OH)D are independently and synergistically associated with a risk for hip fracture in an elderly population: A case control study.

The incidence of hip fractures in Oslo is among the highest in the world. Vitamin D, as well as vitamin K, may play an important role in bone metabolism. We examined if vitamin K1 and 25(OH)D were associated with an increased risk of hip fracture, and whether the possible synergistic effect of these two micronutrients is mediated through bone turnover markers.
Blood was drawn for vitamin K1, 25(OH)D, and the bone turnover marker osteocalcin upon admission for hip fracture and in healthy controls.
Vitamin K1 and 25(OH)D were independently associated with a risk of hip fracture. The adjusted odds ratio (95% CI) per ng/ml increase in vitamin K1 was 0.07 (0.02-0.32), and that per nmol/L increase in 25(OH)D was 0.96 (0.95-0.98). There was a significant interaction between 25(OH)D and vitamin K1 (p < 0.001), and a significant correlation between total osteocalcin and vitamin K1 and 25(OH)D (rho = 0.18, p = 0.01; rho = 0.20, p = 0.01, respectively).
Vitamin K1 and 25(OH)D are lower in hip fracture patients compared with controls. Vitamin K1 and 25(OH)D are independently and synergistically associated with the risk of hip fracture when adjusting for confounders. Intervention studies should include both vitamins.

Torbergsen AC, Watne LO, Wyller TB, Frihagen F…
Clin Nutr Jan 2014
PMID: 24559841

Curcumol Suppresses Osteoclast Formation In Vitro

Abstract

Curcumol suppresses RANKL-induced osteoclast formation by attenuating the JNK signaling pathway.

Osteoclasts, derived from hemopoietic progenitors of the monocyte/macrophage lineage, have a unique role in bone resorption, and are considered a potential therapeutic target in the treatment of such pathologic bone diseases as osteoporosis, rheumatoid arthritis, and periodontitis. In the present study, we demonstrate that curcumol, one of the major components of the essential oil of Rhizoma Curcumae, exhibits an inhibitory effect on receptor activator of nuclear factor kappaB ligand (RANKL)-induced osteoclast differentiation with both bone marrow-derived macrophages and RAW264.7 cells in a dose-dependent manner. In addition, RANKL-induced mRNA expression of osteoclast-specific genes, such as tartrate-resistant acid phosphatase, calcitonin receptor, and cathepsin K, is prominently reduced in the presence of curcumol. Furthermore, the molecular mechanism of action was investigated, and curcumol inhibited osteoclastogenesis by specifically impairing RANKL-induced c-Jun N-terminal kinase (JNK)/activator protein-1 (AP-1) signaling, which was further identified in rescue studies by means of anisomycin, a JNK signaling-specific activator. Taken together, these findings suggest that curcumol suppresses RANKL-induced osteoclast differentiation through the JNK/AP-1 signaling pathway, and may be useful as a therapeutic treatment for bone resorption-associated diseases.

Yu M, Chen X, Lv C, Yi X…
Biochem. Biophys. Res. Commun. Apr 2014
PMID: 24732351

Vitamin E Associated with Increased Bone Density in Postmenopausal Women

Abstract

Lower vitamin E serum levels are associated with osteoporosis in early postmenopausal women: a cross-sectional study.

The aim of this study was to evaluate the relationship between vitamin E status and osteoporosis in early postmenopausal women. Anthropometric data, osteoporosis risk factors, vitamin E serum levels, bone mineral density (BMD) and other serum parameters which may influence bone mineral density in postmenopausal women were analyzed in a cross-sectional study. The association between osteoporosis and age, age of menopause, body mass index, osteocalcin, calcium, vitamin D, vitamin E (measured as 25 hydroxyvitamin D and as α-tocopherol:lipids ratio, respectively), bone alkaline phosphatase, smoking status, leisure physical activity and alcohol intake were modeled by a multivariate logistic regression and multi-linear regression analysis in 232 early postmenopausal women. A lower vitamin E:lipid ratio was associated with osteoporosis in multivariate logistic regression. In a multivariate linear model with BMD of the lumbar spine as a dependent variable, the vitamin E:lipid ratio was clearly related with BMD of the lumbar spine (F ratio = 6.30, p = 0.002). BMD of the lumbar spine was significantly higher in the highest tertile of the vitamin E:lipid ratio than in the lowest tertile. The mean vitamin E:lipid ratio was significantly lower in osteoporotic postmenopausal women (T score ≤-2.5) (3.0 ± 0.6 μmol/mmol) than normal (neither osteoporotic nor osteopenic) postmenopausal women (T score >-1) (3.5 ± 0.7 μmol/mmol) using multivariable-adjusted BMD. These findings highlight that vitamin E may increase BMD in healthy postmenopausal women.

Mata-Granados JM, Cuenca-Acebedo R, Luque de Castro MD, Quesada Gómez JM
J. Bone Miner. Metab. Jul 2013
PMID: 23536191

Citric Acid Increases Bone Density and Strength in Chicks

Abstract

Effect of dietary citric acid on the performance and mineral metabolism of broiler.

The objective of this study was to investigate the effect of dietary citric acid (CA) on the performance and mineral metabolism of broiler chicks. A total of 1720 Ross PM3 broiler chicks (days old) were randomly assigned to four groups (430 in each) and reared for a period of 35 days. The diets of groups 1, 2, 3 and 4 were supplemented with 0%, 0.25%, 0.75% or 1.25% CA by weight respectively. Feed and faeces samples were collected weekly and analysed for acid insoluble ash, calcium (Ca), phosphorus (P) and magnesium (Mg). The pH was measured in feed and faeces. At the age of 28 days, 10 birds from each group were slaughtered; tibiae were collected from each bird for the determination of bone mineral density, total ash, Ca, P, Mg and bone-breaking strength, and blood was collected for the measurement of osteocalcin, serum CrossLaps(®), Ca, P, Mg and 1,25(OH)(2)Vit-D in serum. After finishing the trial on day 37, all chicks were slaughtered by using the approved procedure. Birds that were fed CA diets were heavier (average body weights of 2030, 2079 and 2086 g in the 0.25%, 0.75% and 1.25% CA groups, respectively, relative to the control birds (1986 g). Feed conversion efficiency (weight gain in g per kg of feed intake) was also higher in birds of the CA-fed groups (582, 595 and 587 g/kg feed intake for 0.25%, 0.75% and 1.25% CA respectively), relative to the control birds (565 g/kg feed intake). The digestibility of Ca, P and Mg increased in the CA-fed groups, especially for the diets supplemented with 0.25% and 0.75% CA. Support for finding was also indicated in the results of the analysis of the tibia. At slaughter, the birds had higher carcass weights and higher graded carcasses in the groups that were fed the CA diets. The estimated profit margin was highest for birds fed the diet containing 0.25% CA. Birds of the 0.75% CA group were found to have the second highest estimated profit margin. Addition of CA up to a level of 1.25% of the diet increased performance, feed conversion efficiency, carcass weight and carcass quality, but only in numerical terms. The addition of CA up to 0.75% significantly increased the digestibility of macro minerals, bone ash content, bone mineral density and bone strength of the broiler chicks. It may, therefore, be concluded that the addition of 0.75% CA in a standard diet is suitable for growth, carcass traits, macromineral digestibility and bone mineral density of broiler chicks.

Islam KM, Schaeublin H, Wenk C, Wanner M…
J Anim Physiol Anim Nutr (Berl) Oct 2012
PMID: 22093035