Category Archives: Supplements

Vitamin K1 + D + Minerals Reduced Bone Loss in Postmenopausal Women

Abstract

Vitamin K1 supplementation retards bone loss in postmenopausal women between 50 and 60 years of age.

Although several observational studies have demonstrated an association between vitamin K status and bone mineral density (BMD) in postmenopausal women, no placebo-controlled intervention trials of the effect of vitamin K1 supplementation on bone loss have been reported thus far. In the trial presented here we have investigated the potential complementary effect of vitamin K1 (1 mg/day) and a mineral + vitamin D supplement (8 microg/day) on postmenopausal bone loss. The design of our study was a randomized, double-blind, placebo-controlled intervention study; 181 healthy postmenopausal women between 50 and 60 years old were recruited, 155 of whom completed the study. During the 3-year treatment period, participants received a daily supplement containing either placebo, or calcium, magnesium, zinc, and vitamin D (MD group), or the same formulation with additional vitamin K1 (MDK group). The main outcome was the change in BMD of the femoral neck and lumbar spine after 3 years, as measured by DXA. The group receiving the supplement containing additional vitamin K1 showed reduced bone loss of the femoral neck: after 3 years the difference between the MDK and the placebo group was 1.7% (95% Cl: 0.35-3.44) and that between the MDK and MD group was 1.3% (95% Cl: 0.10-3.41). No significant differences were observed among the three groups with respect to change of BMD at the site of the lumbar spine. If co-administered with minerals and vitamin D, vitamin K1 may substantially contribute to reducing postmenopausal bone loss at the site of the femoral neck.

Braam LA, Knapen MH, Geusens P, Brouns F…
Calcif. Tissue Int. Jul 2003
PMID: 14506950

Low Vitamin K Associated with Fractures in Women, but Not Men

Abstract

Vitamin K intake and bone mineral density in women and men.

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).
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.
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.
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.
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.

Booth SL, Broe KE, Gagnon DR, Tucker KL…
Am. J. Clin. Nutr. Feb 2003
PMID: 12540415 | Free Full Text

Vitamin K2 MK-4 Improves Bone Strength, but Not Density, in Postmenopausal Women

Abstract

Vitamin K2 supplementation improves hip bone geometry and bone strength indices in postmenopausal women.

Vitamin K mediates the synthesis of proteins regulating bone metabolism. We have tested whether high vitamin K(2) intake promotes bone mineral density and bone strength. Results showed that K(2) improved BMC and femoral neck width, but not DXA-BMD. Hence high vitamin K(2) intake may contribute to preventing postmenopausal bone loss.
Vitamin K is involved in the synthesis of several proteins in bone. The importance of K vitamins for optimal bone health has been suggested by population-based studies, but intervention studies with DXA-BMD as a clinical endpoint have shown contradicting results. Unlike BMC, DXA-BMD does not take into account the geometry (size, thickness) of bone, which has an independent contribution to bone strength and fracture risk. Here we have tested whether BMC and femoral neck width are affected by high vitamin K intake.
A randomized clinical intervention study among 325 postmenopausal women receiving either placebo or 45 mg/day of vitamin K(2) (MK-4, menatetrenone) during three years. BMC and hip geometry were assessed by DXA. Bone strength indices were calculated from DXA-BMD, femoral neck width (FNW) and hip axis length (HAL).
K(2) did not affect the DXA-BMD, but BMC and the FNW had increased relative to placebo. In the K(2)-treated group hip bone strength remained unchanged during the 3-year intervention period, whereas in the placebo group bone strength decreased significantly.
Vitamin K(2) helps maintaining bone strength at the site of the femoral neck in postmenopausal women by improving BMC and FNW, whereas it has little effect on DXA-BMD.

Knapen MH, Schurgers LJ, Vermeer C
Osteoporos Int Jul 2007
PMID: 17287908 | Free Full Text

Curcumin + Alendronate Synergy in Ovariectomized Rats

Abstract

A synergistic bone sparing effect of curcumin and alendronate in ovariectomized rat.

The purpose of this study was to evaluate the therapeutic effects of combination therapy with curcumin and alendronate on bone remodeling after ovariectomy in rats.
Eighty female Sprague-Dawley rats underwent either a sham operation (the sham group) or bilateral ovariectomy (OVX). The ovariectomized animals were randomly distributed amongst four groups: untreated OVX group, curcumin-administered group, alendronate-administered group, and the combination therapy group. At 8 and 12 weeks after surgery, rats from each of the groups were euthanized. Serum biochemical markers of bone turnover, including osteocalcin and alkaline phosphatase (ALP), and the telopeptide fragment of type I collagen C-terminus (CTX) were analyzed. Bone histomorphometric parameters of the 4th lumbar vertebrae were determined by micro-computed tomography (CT). In addition, mechanical strength was determined by a three-point bending test.
Serum biochemical markers of bone turnover in the experiment groups (curcumin administered group, alendronate administered group, and the combination therapy group) were significantly lower than in the untreated OVX group (p < 0.05). The combination therapy group had lower ALP and CTX-1 concentrations at 12 weeks, which were statistically significant compared with the curcumin only and the alendronate only group (p < 0.05). The combination therapy group had a significant increase in BMD at 8 weeks and Cr.BMD at 12 weeks compared with the curcumin-only group (p = 0.005 and p = 0.013, respectively). The three point bending test showed that the 4th lumbar vertebrae of the combination therapy group had a significantly greater maximal load value compared to that of the curcumin only and the alendronate only group (p < 0.05).
The present study demonstrated that combination therapy with a high dose of curcumin and a standard dose of alendronate has therapeutic advantages over curcumin or alendronate monotherapy, in terms of the synergistic antiresorptive effect on bone remodeling, and improving bone mechanical strength.

Cho DC, Kim KT, Jeon Y, Sung JK
Acta Neurochir (Wien) Dec 2012
PMID: 23053289

Curcumin Decreases Proliferation and Mineralization of Human Osteoblasts In Vitro

Abstract

Effects of curcumin on the proliferation and mineralization of human osteoblast-like cells: implications of nitric oxide.

Curcumin (diferuloylmethane) is found in the rhizomes of the turmeric plant (Curcuma longa L.) and has been used for centuries as a dietary spice and as a traditional Indian medicine used to treat different conditions. At the cellular level, curcumin modulates important molecular targets: transcription factors, enzymes, cell cycle proteins, cytokines, receptors and cell surface adhesion molecules. Because many of the curcumin targets mentioned above participate in the regulation of bone remodeling, curcumin may affect the skeletal system. Nitric oxide (NO) is a gaseous molecule generated from L-arginine during the catalization of nitric oxide synthase (NOS), and it plays crucial roles in catalization and in the nervous, cardiovascular and immune systems. Human osteoblasts have been shown to express NOS isoforms, and the exact mechanism(s) by which NO regulates bone formation remain unclear. Curcumin has been widely described to inhibit inducible nitric oxide synthase expression and nitric oxide production, at least in part via direct interference in NF-κB activation. In the present study, after exposure of human osteoblast-like cells (MG-63), we have observed that curcumin abrogated inducible NOS expression and decreased NO levels, inhibiting also cell prolifieration. This effect was prevented by the NO donor sodium nitroprusside. Under osteogenic conditions, curcumin also decreased the level of mineralization. Our results indicate that NO plays a role in the osteoblastic profile of MG-63 cells.

Moran JM, Roncero-Martin R, Rodriguez-Velasco FJ, Calderon-Garcia JF…
Int J Mol Sci 2012
PMID: 23443113 | Free Full Text

High-Dose Curcumin Increases Bone Strength and Density in Ovariectomized Rats

Abstract

Therapeutic advantages of treatment of high-dose curcumin in the ovariectomized rat.

Although curcumin has a protective effect on bone remodeling, appropriate therapeutic concentrations of curcumin are not well known as therapeutic drugs for osteoporosis. The purpose of this study was to compare the bone sparing effect of treatment of low-dose and high-dose curcumin after ovariectomy in rats.
Forty female Sprague-Dawley rats underwent either a sham operation (the sham group) or bilateral ovariectomy (OVX). The ovariectomized animals were randomly distributed among three groups; untreated OVX group, low-dose (10 mg/kg) curcumin administered group, and high-dose (50 mg/kg) curcumin group. At 4 and 8 weeks after surgery, serum biochemical markers of bone turnover were analyzed. Bone histomorphometric parameters of the 4th lumbar vertebrae were determined by micro-computed tomography (CT). In addition, mechanical strength was determined by a three-point bending test.
High-dose curcumin group showed significantly lower osteocalcin, alkaline phosphatase, and the telopeptide fragment of type I collagen C-terminus concentration at 4 and 8 weeks compared with the untreated OVX group as well as low-dose curcumin group. In the analyses of micro-CT scans of 4th lumbar vertebrae, the high-dose curcumin treated group showed a significant increase in bone mineral densities (p=0.028) and cortical bone mineral densities (p=0.036) compared with the low-dose curcumin treated group. Only high-dose curcumin treated group had a significant increase of mechanical strength compared with the untreated OVX group (p=0.015).
The present study results demonstrat that a high-dose curcumin has therapeutic advantages over a low-dose curcumin of an antiresorptive effect on bone remodeling and improving bone mechanical strength.

Cho DC, Jung HS, Kim KT, Jeon Y…
J Korean Neurosurg Soc Dec 2013
PMID: 24527187 | Free Full Text

Curcumin Helps Kill Osteoblasts In Vitro

Abstract

Dosage effects of curcumin on cell death types in a human osteoblast cell line.

Curcumin, the yellow pigment of Curcuma longa, is known to have antioxidant and anti-inflammatory properties, as well as their ability to either induce or prevent cell apoptosis. However, the precise molecular mechanisms of these effects are unknown. Here, we demonstrate that curcumin can induce apoptotic changes, including JNK activation, caspase-3 activation, and cleavage of PARP and PAK2, at treatment concentrations lower than 25 microM in human osteoblast cells. In contrast, treatment with 50-200 microM of curcumin does not induce apoptosis, but rather triggers necrotic cell death in human osteoblasts. Using the cell permeable dye 2′,7′-dichlorofluorescin diacetate (DCF-DA) as an indicator of reactive oxygen species (ROS) generation, we found that while treatment with 12.5-25 microM curcumin directly increased intracellular oxidative stress, 50-200 microM curcumin had far less effect. Pretreatment of cells with N-acetyl cysteine or alpha-tocopherol, two well known ROS scavengers, attenuated the intracellular ROS levels increases and converted the apoptosis to necrosis induced by 12.5-25 microM curcumin. Moreover, we observed a dose-dependent decrease in intracellular ATP levels after treatment of osteoblast cells with curcumin and pretreatment of cells with antimycin or 2-deoxyglucose to cause ATP depletion significantly converted 12.5-25 microM curcumin-induced apoptosis to necrosis, indicating that ATP (a known mediator of apoptotic versus necrotic death) is most likely involved in the switching mechanism. Overall, our results signify that curcumin dosage treatment determines the possible effect on ROS generation, intracellular ATP levels, and cell apoptosis or necrosis in osteoblast cells.

Chan WH, Wu HY, Chang WH
Food Chem. Toxicol. Aug 2006
PMID: 16624471

Curcumin Decreases Bone Density in Rats

Abstract

Effects of curcumin on the skeletal system in rats.

There is increasing interest in the discovery of natural compounds that could favorably affect the skeletal system. Curcumin is a constituent of turmeric, a plant which has been used for centuries as a dietary spice and a traditional Indian medicine. Curcumin has been reported to affect differentiation, activity and the lifespan of osteoblasts and osteoclasts in vitro. The aim of the present study was to investigate the effects of curcumin on the skeletal system of rats in vivo. Curcumin (10 mg/kg, po daily) was administered for four weeks to normal (non-ovariectomized) and bilaterally ovariectomized (estrogen-deficient) three-month-old female Wistar Cmd:(WI)WU rats. Ovariectomy was performed seven days before the start of curcumin administration. Bone mass, mineral and calcium content, macrometric and histomorphometric parameters, as well as the mechanical properties of the bone, were examined. Serum total cholesterol and estradiol levels were also determined. In rats with normal estrogen levels, curcumin decreased serum estradiol level and slightly increased cancellous bone formation, along with decreased mineralization. Estrogen deficiency induced osteoporotic changes in the skeletal system of the ovariectomized control rats. In ovariectomized rats, curcumin decreased body mass gain and serum total cholesterol level, slightly improved some bone histomorphometric parameters impaired by estrogen deficiency, but did not improve bone mineralization or mechanical properties. In conclusion, the results of the present in vivo study in rats did not support the hypothesis that curcumin, at doses that are readily achievable through dietary intake, could be useful for the prevention or treatment of osteoporosis.

Folwarczna J, Zych M, Trzeciak HI
Pharmacol Rep
PMID: 21098873 | Free Full Text

Curcumin Prevents Bone Loss in Ovariectomized Rats

Abstract

Curcumin protects against ovariectomy-induced bone loss and decreases osteoclastogenesis.

Curcumin has anti-oxidative activity. In view of the increasing evidence for a biochemical link between increased oxidative stress and reduced bone density we hypothesized that curcumin might increase bone density by elevating antioxidant activity in some target cell type. We measured bone density by Micro-CT, enzyme expression levels by quantitative PCR or enzyme activity, and osteoclast (OC) formation by tartrate-resistant acid phosphatase staining. The bone mineral density of the femurs of curcumin-administered mice was significantly higher than that of vehicle-treated mice after ovariectomy (OVX) and this was accompanied by reduced amounts of serum collagen-type I fragments, which are markers of bone resorption. Curcumin suppressed OC formation by increasing receptor activator of nuclear factor-κB ligand (RANKL)-induced glutathione peroxidase-1, and reversed the stimulatory effect of homocysteine, a known H(2) O(2) generator, on OC formation by restoring Gpx activity. Curcumin generated an aberrant RANKL signal characterized by reduced expression of nuclear factor of activated T cells 2 (NFAT2) and attenuated activation of mitogen-activated protein kinases (ERK, JNK, and p38). Curcumin thus inhibited OVX-induced bone loss, at least in part by reducing osteoclastogenesis as a result of increased antioxidant activity and impaired RANKL signaling. These findings suggest that bone loss associated with estrogen deficiency could be attenuated by curcumin administration.

Kim WK, Ke K, Sul OJ, Kim HJ…
J. Cell. Biochem. Nov 2011
PMID: 21732406

The ovariectomized, mature rat model of postmenopausal osteoporosis: an assessment of the bone sparing effects of curcumin.

Abstract

The ovariectomized, mature rat model of postmenopausal osteoporosis: an assessment of the bone sparing effects of curcumin.

Identification of natural health products that might benefit skeletal health could reduce the negative impact of osteoporotic bone fractures upon society. The objectives of this study were to evaluate an animal model of postmenopausal osteoporosis and to search for evidence that curcumin reduces bone mineral losses in a dose-dependent manner when endogenous estrogen levels are reduced. Bone mineral density was measured at the spine, femur and whole body before and at 2, 4 and 6 months after ovariectomy in each of 40 mature rats. Serum osteocalcin and C-telopeptide were measured as indicators of bone formation and resorption rates. Femoral compressive strength was measured at 6 months. Ovariectomy alone resulted in loss of mineral from the spine (p<0.005) and an increase in osteocalcin levels (p<0.05). At the same time, there was an increase in energy to fracture (p<0.01) due to an increased bone size. When ovariectomized animals were given etidronate there was no loss of mineral from the spine, the size of the femur increased (p<0.005), C-telopeptide levels were reduced (p<0.001) and femoral compressive strength increased (p<0.025). Administration of curcumin to ovariectomized animals resulted in changes that were intermediate between those produced by etidronate and by ovariectomy alone. The increase in femur size produced by the highest dose of curcumin was statistically significant (p< 0.01) and curcumin administration resulted in a significant, dose dependent, increase in energy to fracture. Curcumin produces beneficial changes in bone turnover and increases in bone strength using the ovariectomized mature rat model of postmenopausal osteoporosis.

French DL, Muir JM, Webber CE
Phytomedicine Dec 2008
PMID: 18693096