Category Archives: Supplements

Magnesium Water No Benefit in Postmenopausal Women

Abstract

A double-blind, placebo-controlled study of the short term effects of a spring water supplemented with magnesium bicarbonate on acid/base balance, bone metabolism and cardiovascular risk factors in postmenopausal women.

A number of health benefits including improvements in acid/base balance, bone metabolism, and cardiovascular risk factors have been attributed to the intake of magnesium rich alkaline mineral water. This study was designed to investigate the effects of the regular consumption of magnesium bicarbonate supplemented spring water on pH, biochemical parameters of bone metabolism, lipid profile and blood pressure in postmenopausal women. In this double-blind, placebo-controlled, parallel-group, study, 67 postmenopausal women were randomised to receive between 1500 mL and 1800 mL daily of magnesium bicarbonate supplemented spring water (650 mg/L bicarbonate, 120 mg/L magnesium, pH 8.3-8.5) (supplemented water group) or spring water without supplements (control water group) over 84 days. Over this period biomarkers of bone turnover (serum parathyroid hormone (PTH), 1,25-dihydroxyvitamin D, osteocalcin, urinary telopeptides and hydroxyproline), serum lipids (total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides), venous and urinary pH were measured together with measurements of standard biochemistry, haematology and urine examinations. Serum magnesium concentrations and urinary pH in subjects consuming the magnesium bicarbonate supplemented water increased significantly at Day 84 compared to subjects consuming the spring water control (magnesium – p = 0.03; pH – p = 0.018). The consumption of spring water led to a trend for an increase in parathyroid hormone (PTH) concentrations while the PTH concentrations remained stable with the intake of the supplemented spring water. However there were no significant effects of magnesium bicarbonate supplementation in changes to biomarkers of bone mineral metabolism (n-telopeptides, hydroxyproline, osteocalcin and 1,25-dihydroxyvitamin D) or serum lipids or blood pressure in postmenopausal women from Day 0 to Day 84.
Short term regular ingestion of magnesium bicarbonate supplemented water provides a source of orally available magnesium. Long term clinical studies are required to investigate any health benefits.

Day RO, Liauw W, Tozer LM, McElduff P…
BMC Res Notes 2010
PMID: 20579398 | Free Full Text

The acid/base theory is questionable and this was a low dose of Magnesium.

Review: Vitamin A Increases Fracture Risk at 2x Recommended Intake

Abstract

Vitamin A intake and osteoporosis: a clinical review.

If osteoporosis is linked with vitamin A (Vit A) A consumption, millions of people could be affected. A MEDLINE search was performed with keywords retinol, beta-carotene, and osteoporosis. Of 20 clinical studies, 3 were randomized controlled trials (RCTs), 14 were observational studies, and 3 were case reports. Most (8) observational studies were cross-sectional. Oral retinoyl palmitate (RP) in high doses induces fractures and radiographic osteoporosis in animals. Retinol intake from diet or supplements is negatively associated with lumbar, femoral neck, and trochanter bone mineral density (BMD). There is a graded increase in relative risk of hip fracture with increasing retinol intake, attributable primarily to retinol (either from diet or supplements) but not beta-carotene intake. Higher serum retinol levels are associated with higher risk of any fracture and with higher risk of hip fracture, whereas there is no evidence of harm associated with beta-carotene intake. The few RCTs involve serum markers of bone metabolism, not bone density or fracture outcomes. Observational studies are generally consistent in finding harm from either dietary or supplemental retinol intake on BMD and hip fracture risk. Total Vit A intake is more important than source in determining harm. Adverse effects may occur at a level of retinol intake that is only about twice the current recommendation for adult females.
It is not yet possible to set a specific level of retinol intake above which bone health is compromised. Pending further investigation, Vit A supplements should not be used with the express goal of improving bone health.

Crandall C
J Womens Health (Larchmt) Oct 2004
PMID: 15671709

The recommended dietary allowance (RDA) for Vitamin as preformed Vitamin A (Retinol Activity Equivalents) is 700 mcg (or 2,333 IU). This article suggests that twice that, or 4666 IU, increases fracture risk.

Vitamin A Not Associated with Bone Density or Fracture in 2016 Perimenopausal Danish Women

Abstract

No effect of vitamin A intake on bone mineral density and fracture risk in perimenopausal women.

In recent studies from Sweden and the United States, a high vitamin A intake has been associated with low bone mineral density (BMD) and increased fracture risk. In Sweden and the United States, food items such as milk and breakfast cereals are fortified with vitamin A, whereas in Denmark there is no mandatory fortification with vitamin A. In the present study, we investigated relations between vitamin A intake and BMD and fracture risk in a Danish population consuming mostly unfortified food items. Within a population-based cohort study in 2,016 perimenopausal women, associations between BMD and vitamin A intake were assessed at baseline and after 5-year follow-up. Moreover, associations between baseline vitamin A intake and 5-year changes in BMD were studied. Finally, fracture risk was assessed in relation to vitamin A intake. In our cohort, dietary retinol intake (0.53 mg/day) was lower than the intake reported in recent studies form Sweden (0.78 mg/day) and the United States (1.66 mg/day). Cross-sectional and longitudinal analyses showed no associations between intake of vitamin A and BMD of the femoral neck or lumbar spine. Neither did BMD differ between those 5% who had the highest, and those 5% who had the lowest, vitamin A intake. During the 5-year study period, 163 subjects sustained a fracture (cases). Compared to 978 controls, logistic regression analyses revealed no difference in vitamin A intake. Thus, in a Danish population, average vitamin A intake is lower than in Sweden and the United States and not associated with detrimental effects on bone.

Rejnmark L, Vestergaard P, Charles P, Hermann AP…
Osteoporos Int Nov 2004
PMID: 15034644

Korean Black Raspberry Enhances Osteoblast Function In Vitro

Abstract

Rubus coreanus Miq. extract promotes osteoblast differentiation and inhibits bone-resorbing mediators in MC3T3-E1 cells.

To prevent bone loss that occurs with increasing age, certain nutritional and pharmacological factors are needed. In the present study, the ethanol extract from the fruit of Rubus coreanus Miq. (RCE) was investigated for its effect on the function of osteoblastic MC3T3-E1 cells. RCE (10approximately50 microg/ml) caused a significant elevation in cell viability, alkaline phosphatase (ALP) activity, collagen content, and osteocalcin secretion in the cells. The effect of RCE (50 microg/ml) in increasing cell viability, ALP activity, and collagen content was prevented by the presence of 10(-6) M cycloheximide and 10(-6) M tamoxifen, suggesting that RCE’s effect results from a newly synthesized protein component and might be partly involved in estrogen action. We then examined the effect of RCE on the H(2)O(2)-induced apoptosis and production of local factors in osteoblasts. Treatment with RCE (10approximately50 microg/ml) decreased the 0.2 mM H(2)O(2)-induced apoptosis and production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and nitric oxide (NO) in osteoblasts. Our data indicate that the enhancement of osteoblast function by Rubus coreanus Miq. may result in the prevention of osteoporosis and inflammatory bone diseases.

Lee KH, Choi EM
Am. J. Chin. Med. 2006
PMID: 16883635

Korean Black Raspberry Increases Osteoblasts and Apoptosis of Osteoclasts in Ovariectomized Rats

Abstract

Bone-protecting effect of Rubus coreanus by dual regulation of osteoblasts and osteoclasts.

Bone loss occurs with increasing age and/or as a secondary occurrence to chronic metabolic disease. Certain nutritional and pharmacological, as well as nonpharmacologic interventions such as weight-bearing exercise and muscle strengthening help prevent bone loss. We examined the effect of the methanol extract from the fruit of Rubus coreanus (RCM) on postmenopausal osteoporosis.
Ovariectomized rats were assigned to sham (negative control), vehicle control, positive control, safflower seed 200 mg/kg, RCM 100 mg/kg (RCM 100), RCM 200 mg/kg (RCM 200), and RCM 400 mg/kg (RCM 400) groups for 10 weeks after the operation. Serum biochemistry, histochemistry, immunohistochemistry, and other related biomarkers of bone metabolism were investigated.
We observed that RCM could prevent bone loss by increasing the femur trabecular bone area in a dose-dependent manner in ovariectomized rats. The mineral composition of RCM contains many more valuable elements, especially potassium, magnesium, and vitamins D and B2, than safflower seed. The effect of RCM increased not only osteoblast differentiation but also osteoclast apoptosis. In addition, the extract of RCM contained in quercetin suggests that the extract of RCM resulted in improved aging-related bone loss through an antioxidant effect.
The present data provide the first direct in vivo evidence that RCM has a bone-protecting effect caused by estrogen deficiency, without undesirable side effects on the uterus and other solid organs. The beneficial effect of RCM may be mediated, at least in part, by dual regulation of the enhancement of osteoblast function and induction of osteoclast apoptosis.

Do SH, Lee JW, Jeong WI, Chung JY…
Menopause
PMID: 18709701

Sodium Associated with Higher Bone Density

Abstract

Dietary sodium and bone mineral density: results of a 16-year follow-up study.

It has been proposed that high dietary sodium intake, resulting in a sodium-mediated increase in renal calcium excretion, is a risk factor for osteoporosis. To evaluate the relationship between dietary sodium intake and bone mineral density (BMD), a prospective study of the Rancho Bernardo cohort was performed. A 24-hour diet recall was done for the period 1973 through 1975; follow-up bone mineral density of the ultradistal radius, midradius, total hip, and spine was measured between 1988 and 1991. Covariates were ascertained by self-report and examination at baseline. Multivariable analysis of the sodium-BMD association was performed using gender and menopause-specific linear regressions.
All subjects were white. At the bone evaluation, there were 258 women (average age 73.3 years) and 169 men (average age 72.4 years). In both men and women, higher levels of sodium intake were strongly associated with higher levels of calcium intake and total calories. Body mass index increased with sodium quartile in women, while a modest negative association was seen in men. In women, after age adjustment, positive associations between dietary sodium and bone density were found at the ultradistal radius (beta = 0.01, P = 0.03) and the total hip (beta = 0.019, P = 0.02). BMD increased by 0.01 to 0.02 g/cm2 per gram increase in sodium ingested. After adjustment for estrogen use, body mass, dietary calcium, alcohol, and total calories, these effects were no longer significant. Similar patterns were seen in pre- and postmenopausal women. In men, age and multivariate-adjusted BMD increased with higher sodium intake at the ultradistal radius only (beta = 0.013, P = 0.05). Stratification by gender-specific median calcium level did not significantly effect the results.
After control for confounders, a small, statistically significant protective effect of sodium was found at the ultradistal radius in men only. At other sites in women and men, no effect of sodium on BMD was apparent in the multivariable models. These results do not support a detrimental effect of dietary sodium on bone mineral density. Rather, the findings suggest that sodium intake, in the range measured, is not a major osteoporosis risk factor.

Greendale GA, Barrett-Connor E, Edelstein S, Ingles S…
J Am Geriatr Soc Oct 1994
PMID: 7930328

Oligogalacturonic Acid Inhibits Resorption In Vitro

Abstract

Oligogalacturonic acid inhibit bone resorption and collagen degradation through its interaction with type I collagen.

In this study, we showed that oligogalacturonic acid (OGA) purified from flax pectin inhibit in vitro osteoclastic bone resorption in a dose-dependent manner. The OGA inhibitory effect was neither linked to an effect on osteoclast apoptosis, nor to an inhibition of cathepsin K activity. By means of an in vitro collagen degradation assay we demonstrated that OGA prevented triple-helical type I collagen cleavage by cathepsin K in a dose and chain length dependent manner. This inhibition was not restricted to cathepsin K, since collagenolytic activity of other lysosomal cysteine proteases, such as cathepsin B and cathepsin L, as well as matrixmetalloproteinases such as MMP-9 were also inhibited. Interestingly, using non-collagen substrates we demonstrated that OGA does not inhibit the proteolytic activity of cathepsin B and L, suggesting that OGA inhibits collagen degradation without affecting the lysosomal cysteine enzyme proteolytic activity. Finally, preliminary study using surface plasmon resonance (SPR) showed that OGA binds to type I collagen but not to albumin, consistent with a specific effect on collagen. These results suggest that the observed inhibition of collagen degradation by OGA may be due to its ability to bind to the collagen molecule. By masking the collagen surface, OGA may render the collagen cleavage site less accessible to enzymes and thus prevent its enzymatic degradation.

Lion JM, Mentaverri R, Rossard S, Jullian N…
Biochem. Pharmacol. Dec 2009
PMID: 19647720

Eldecalcitol > Alfacalcidol in Ovariectomized Rats

Abstract

Effects of combined treatment with eldecalcitol and alendronate on bone mass, mechanical properties, and bone histomorphometry in ovariectomized rats: a comparison with alfacalcidol and alendronate.

Eldecalcitol (ELD), a 2β-hydroxypropyloxy derivative of 1α,25 (OH) 2D3, inhibits bone resorption more potently than alfacalcidol (ALF) while maintaining osteoblastic function in an ovariectomized (OVX) osteoporosis rat model. Alendronate (ALN), which is the most common bisphosphonate used for the treatment of osteoporosis, increases the bone mineral density (BMD) by suppressing bone resorption. In this study, we investigated the effects of combination treatments with ELD and ALN or with ALF and ALN on bone mass and strength in OVX rats. Seventy female rats, 32 weeks old, were assigned to seven groups: (1) a sham-operated control group; (2) an OVX-control group; (3) an ELD group; (4) an ALF group; (5) an ALN group; (6) an ELD+ALN group; and (7) an ALF+ALN group. OVX rats were orally treated with ELD (0.015 μg/kg), ALF (0.0375 μg/kg), or ALN (0.2mg/kg) daily for 12 weeks. In both the lumbar spine and the femur, ELD and ALF monotherapy significantly increased the BMD, and ELD+ALN and ALF+ALN significantly increased the BMD, compared with ALN monotherapy, as an additive effect. In particular, ELD+ALN resulted in a significantly higher BMD than ALF+ALN in the femur. On mechanical testing of the lumbar spine, ELD and ALF monotherapy significantly increased the ultimate load, and ELD+ALN and ALF+ALN significantly increased the ultimate load compared with ALN monotherapy. In the femur, ELD, ELD+ALN, and ALF+ALN treatment significantly increased the ultimate load, compared with the OVX-control group, and ELD+ALN resulted in a significantly higher ultimate load than ALN monotherapy. A histomorphometric analysis showed that ELD monotherapy and ELD+ALN combination therapy had a potent inhibitory effect on bone resorption parameters (osteoclast surface and eroded surface), while maintaining bone formation parameters (osteoblast surface and osteoid surface). By contrast, ALF and ALF+ALN significantly lowered the histological parameters of both bone resorption and formation. These results suggested that ELD or ALF used in combination with ALN has therapeutic advantages over ALN monotherapy, with ELD+ALN combination treatment producing an especially beneficial anti-osteoporotic effect by inhibiting osteoclastic bone resorption and maintaining osteoblastic function, compared with ALF+ALN combination treatment.

Sugimoto M, Futaki N, Harada M, Kaku S
Bone Jan 2013
PMID: 23041510

Low Dose MK-4 for a Year Maintains Bone Density and Improves Bone Quality in Postmenopausal Japanese Women

Abstract

Low-dose vitamin K2 (MK-4) supplementation for 12 months improves bone metabolism and prevents forearm bone loss in postmenopausal Japanese women.

Menaquinone-4 (MK-4) administered at a pharmacological dosage of 45 mg/day has been used for the treatment of osteoporosis in Japan. However, it is not known whether a lower dose of MK-4 supplementation is beneficial for bone health in healthy postmenopausal women. The aim of this study was to examine the long-term effects of 1.5-mg daily supplementation of MK-4 on the various markers of bone turnover and bone mineral density (BMD). The study was performed as a randomized, double-blind, placebo-controlled trial. The participants (aged 50-65 years) were randomly assigned to one of two groups according to the MK-4 dose received: the placebo-control group (n = 24) and the 1.5-mg MK-4 group (n = 24). The baseline concentrations of undercarboxylated osteocalcin (ucOC) were high in both groups (>5.1 ng/ml). After 6 and 12 months, the serum ucOC concentrations were significantly lower in the MK-4 group than in the control group. In the control group, there was no significant change in serum pentosidine concentrations. However, in the MK-4 group, the concentration of pentosidine at 6 and 12 months was significantly lower than that at baseline. The forearm BMD was significantly lower after 12 months than at 6 months in the control group. However, there was no significant decrease in BMD in the MK-4 group during the study period. These results suggest that low-dose MK-4 supplementation for 6-12 months improved bone quality in the postmenopausal Japanese women by decreasing the serum ucOC and pentosidine concentrations, without any substantial adverse effects.

Koitaya N, Sekiguchi M, Tousen Y, Nishide Y…
J. Bone Miner. Metab. Mar 2014
PMID: 23702931

This study appears to be a continuation of this 4 week study: Low Dose MK-4 May Benefit Bones in Postmenopausal Japanese Women

Vitamin K1 Associated With Bone Health in Women

Abstract

Vitamin K1 intake is associated with higher bone mineral density and reduced bone resorption in early postmenopausal Scottish women: no evidence of gene-nutrient interaction with apolipoprotein E polymorphisms.

Polymorphisms in the apolipoprotein E (APOE) gene are associated with fracture risk, and a potential mechanism is through vitamin K transport.
We investigated the relation between dietary vitamin K(1) intake, APOE polymorphisms, and markers of bone health. We measured bone mineral density (BMD) at the lumbar spine (LS) and femoral neck (FN) in a cohort of Scottish women aged 49-54 y in 1990-1994 (baseline) and in 1997-2000 (visit 2). At visit 2, bone markers (urinary pyridinoline crosslinks and serum N-terminal propeptide of type 1 collagen) were measured, 3199 women completed a food-frequency questionnaire, and 2721 women were genotyped for APOE.
Compared with quartile 3 (Q3) of energy-adjusted vitamin K(1) intake (mean: 116 microg/d), women in the lowest quartile (mean: 59 microg/d) had lower BMD (analysis of variance; FN, Q1: 0.831 +/- 0.122 g/cm(2); Q3: 0.850 +/- 0.126 g/cm(2); P < 0.001; LS, Q1: 1.000 +/- 0.170 g/cm(2); Q3: 1.020 +/- 0.172 g/cm(2); P = 0.009), remaining significant at the FN after adjustment for age, weight, height, menopausal status or use of hormone replacement therapy, socioeconomic status, and physical activity (P = 0.04). Vitamin K(1) intake was associated with reduced concentrations of pyridinoline crosslinks (Q1: 5.4 +/- 2.0 nmol/mmol; Q4: 5.1 +/- 1.9 nmol/mmol; P = 0.003). Carriers of the E2 allele had greater LS BMD at visit 2 and lost less BMD than did carriers of the E4 allele (E2: -0.50 +/- 1.22%/y; E4: -0.71 +/- 1.17%/y; P = 0.05). After adjustment for confounders, the P value for BMD loss (0.03 for LS and 0.04 for FN) did not reach the level of significance required for multiple testing (P = 0.012). No interaction was observed between dietary vitamin K and APOE on BMD.
Vitamin K(1) intake was associated with markers of bone health, but no interaction was observed with APOE alleles on BMD or markers of bone turnover.

Macdonald HM, McGuigan FE, Lanham-New SA, Fraser WD…
Am. J. Clin. Nutr. May 2008
PMID: 18469278 | Free Full Text