Tag Archives: human

Vitamin K1 and MK-4 Stimulate Osteoblasts and Inhibit Osteoclasts In Vitro

Abstract

Vitamin K stimulates osteoblastogenesis and inhibits osteoclastogenesis in human bone marrow cell culture.

Accumulating evidence indicates that menaquinone-4 (MK-4), a vitamin K(2) with four isoprene units, inhibits osteoclastogenesis in murine bone marrow culture, but the reason for this inhibition is not yet clear, especially in human bone marrow culture. To clarify the inhibitory mechanism, we investigated the differentiation of colony-forming-unit fibroblasts (CFU-Fs) and osteoclasts in human bone marrow culture, to learn whether the enhancement of the differentiation of CFU-Fs from progenitor cells might relate to inhibition of osteoclast formation. Human bone marrow cells were grown in alpha-minimal essential medium with horse serum in the presence of MK-4 until adherent cells formed colonies (CFU-Fs). Colonies that stained positive for alkaline phosphatase activity (CFU-F/ALP(+)) were considered to have osteogenic potential. MK-4 stimulated the number of CFU-F/ALP(+) colonies in the presence or absence of dexamethasone. The stimulation was also seen in vitamin K(1) treatment. These cells had the ability to mineralize in the presence of alpha-glycerophosphate. In contrast, both MK-4 and vitamin K(1) inhibited 1,25 dihydroxyvitamin D(3)-induced osteoclast formation and increased stromal cell formation in human bone marrow culture. These stromal cells expressed ALP and Cbfa1. Moreover, both types of vitamin K treatment decreased the expression of receptor activator of nuclear factor kappaB ligand/osteoclast differentiation factor (RANKL/ODF) and enhanced the expression of osteoprotegerin/osteoclast inhibitory factor (OPG/OCIF) in the stromal cells. The effective concentrations were 1.0 microM and 10 microM for the expression of RANKL/ODF and OPG/OCIF respectively. Vitamin K might stimulate osteoblastogenesis in bone marrow cells, regulating osteoclastogenesis through the expression of RANKL/ODF more than through that of OPG/OCIF.

Koshihara Y, Hoshi K, Okawara R, Ishibashi H…
J. Endocrinol. Mar 2003
PMID: 12630919 | Free Full Text

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 Evidence is Mixed

Abstract

Vitamin K and bone health in older adults.

Vitamin K is one of several nutrients that have been linked with bone health. In particular, there is an emerging literature regarding the questionable efficacy of vitamin K supplementation in reducing age-related bone loss. This review aims to summarize the role of vitamin K in bone health in older adults and discuss the clinical implications from a select few human studies. The evidence for vitamin K supplementation in older adults is mixed. Although the observational studies have shown linkages between vitamin K intake and lower risk of fractures in this population, the current evidence from randomized controlled trials is not strongly supportive of vitamin K supplementation in older adults for the intent of improving bone health.

Shah K, Gleason L, Villareal DT
J Nutr Gerontol Geriatr 2014
PMID: 24597993

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 at 600mcg for 6 Months Doesn’t Significantly Increase Bone Density in Women

Abstract

Vitamin K supplementation does not significantly impact bone mineral density and biochemical markers of bone in pre- and perimenopausal women.

Because of its role in osteoblastic metabolism, vitamin K has been studied with respect to bone. However, there has been limited research examining the influence of long-term vitamin K supplementation on bone mineral density (BMD). Therefore, the purpose of this study was to assess the impact of 6 months of vitamin K supplementation on BMD and biomarkers of bone in pre- and perimenopausal women. Based on previous work, we hypothesized that vitamin K would improve BMD and biochemical markers of bone formation. A double-blind, placebo-controlled, randomized trial is an effective way to study the impact of long-term supplementation. Thus, 14 pre- and perimenopausal women, 25 to 50 years of age, were randomly assigned to an experimental group (E) that received 600 microg/d of vitamin K in the form of phylloquinone (K(1)) or a control group (C) that received identical-looking placebo tablets. Regional BMD and percent body fat, measured by dual-energy x-ray absorptiometry, and serum osteocalcin and urinary N-telopeptide levels were all assessed at 0, 3, and 6 months. When BMD was measured across time, C had a significant increase (P = .011) in greater trochanter BMD compared to E. The E group had a nonsignificant increase (P = .067) in shaft BMD compared to the C group. There was no significant difference between E and C in serum osteocalcin concentrations over time. Urinary N-telopeptide levels increased significantly over time in E compared to C (P = .008). Six months of 600 microg/d vitamin K(1) supplementation did not improve regional BMD in this group of pre- and perimenopausal women.

Volpe SL, Leung MM, Giordano H
Nutr Res Sep 2008
PMID: 19083462

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

Review: Vitamin K and Bone Health in Postmenopausal Women

Abstract

Effects of vitamin K in postmenopausal women: mini review.

Possible benefits of vitamin K on bone health, fracture risk, markers of bone formation and resorption, cardiovascular health, and cancer risk in postmenopausal women have been investigated for over three decades; yet there is no clear evidence-based universal recommendation for its use. Interventional studies showed that vitamin K1 provided significant improvement in undercarboxylated osteocalcin (ucOC) levels in postmenopausal women with normal bone mineral density (BMD); however, there are inconsistent results in women with low BMD. There is no study showing any improvement in bone-alkaline-phosphatase (BAP), n-telopeptide of type-1 collagen (NTX), 25-hydroxy-vitamin D, and urinary markers. Improvement in BMD could not be shown in the majority of the studies; there is no interventional study evaluating the fracture risk. Studies evaluating the isolated effects of menatetrenone (MK-4) showed significant improvement in osteocalcin (OC); however, there are inconsistent results on BAP, NTX, and urinary markers. BMD was found to be significantly increased in the majority of studies. The fracture risk was assessed in three studies, which showed decreased fracture risk to some extent. Although there are proven beneficial effects on some of the bone formation markers, there is not enough evidence-based data to support a role for vitamin K supplementation in osteoporosis prevention among healthy, postmenopausal women receiving vitamin D and calcium supplementation. Interventional studies investigating the isolated role of vitamin K on cardiovascular health are required. Longterm clinical trials are required to evaluate the effect of vitamin K on gynecological cancers. MK-4 seems safe even at doses as high as 45 mg/day.

Guralp O, Erel CT
Maturitas Mar 2014
PMID: 24342502

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

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

Lowering Sodium Increases the Effect of Calcium to Reduce Bone Loss in 124 Postmenopausal Women

Abstract

A longitudinal study of the effect of sodium and calcium intakes on regional bone density in postmenopausal women.

The influence of urinary sodium excretion and dietary calcium intake was examined in a 2-y longitudinal study of bone density in 124 women postmenopausal for > 10 y. Analysis of bone density changes showed that urinary sodium excretion was negatively correlated with changes in bone density at the intertrochanteric and total hip sites. Multiple-regression analysis of dietary calcium intake and urine sodium excretion on the change in bone density showed that both dietary calcium and urinary sodium excretion were significant determinants of the change in bone mass over 2 y at the hip and ankle sites. These data suggest that an effect of reducing bone loss equivalent to that achieved by a daily dietary increase of 891 mg (22 mmol) Ca can also be achieved by halving daily sodium excretion. No bone loss occurred at the total hip site at a calcium intake of 1768 mg/d (44 mmol/d) or a urine sodium excretion of 2110 mg/d (92 mmol/d). We report a significant effect of sodium excretion on bone loss in this population.

Devine A, Criddle RA, Dick IM, Kerr DA…
Am. J. Clin. Nutr. Oct 1995
PMID: 7572702 | Free Full Text