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Moderate Alcohol is Good; Caffeine with Low Calcium is Bad

Abstract

To drink or not to drink: how are alcohol, caffeine and past smoking related to bone mineral density in elderly women?

To determine relationship between alcohol, caffeine, past smoking and bone mineral density of different skeletal sites in elderly women, accounting for other biological and life-style variables.
A cross-sectional study in 136 Caucasian women, mean +/- SD age 68.6 +/- 7.1 years, all healthy and free of medications affecting bones, including estrogen. Bone mineral density (BMD) of multiple skeletal regions and body composition were measured by dual X-ray absorptiometry. Serum vitamin D (25-OHD) and parathyroid hormone (PTH) were analyzed and used as confounders. Calcium (Ca) intake was assessed by food frequency questionnaire. Alcohol and caffeine consumption was assessed by questionnaires determining frequency, amount and source of each. There were no current smokers, but the history of smoking was recorded, including number of years and packages smoked/day. Past physical activity was assessed by Allied Dunbar National Fitness Survey and used as confounder. Statistical significance was considered at p <or= 0.05.
In the correlational analysis, alcohol was positively associated with spine BMD (r = 0.197, p = 0.02), 25-OHD and negatively with PTH. Smoking was negatively related to Ca intake, 25(OH)D and number of reproductive years. In subgroup (stratified by Ca intake) and multiple regression analyses, alcohol (average approximately 0.5-1 drinks/day or approximately 8 g alcohol/day) was favorably associated with BMD of spine and total body. Caffeine (average approximately 2.5 6-fl oz cups/day or 200-300 mg caffeine/day) had negative association with most of the skeletal sites, which was attenuated with higher Ca intake (>or=median, 750 mg/day). The past smokers who smoked on average 24 years of approximately 1 pack cigarettes/day had lower BMD in total body, spine and femur than never-smokers when evaluated in subgroup analyses, and the association was attenuated in participants with >or=median Ca intake. There was no significant association between past smoking and BMD of any skeletal site in multiple regression analyses.
The results support the notion that consumption of small/moderate amount of alcohol is positively, while caffeine and past smoking are negatively associated with most of the skeletal sites, which might be attenuated with Ca intake above 750 mg/day.

Ilich JZ, Brownbill RA, Tamborini L, Crncevic-Orlic Z
J Am Coll Nutr Dec 2002
PMID: 12480799


It is interesting how many things are bad when calcium is low. There is some evidence that high protein, caffeine, and sodium are all bad for bones only when calcium is low. Otherwise, they all may be moderately good for bones when calcium is high.

 

Propolis Inhibits IL-17

Abstract

Suppression of interleukin 17 production by Brazilian propolis in mice with collagen-induced arthritis.

Propolis is a resinous substance collected by honeybees from leaf buds and cracks in the bark of various plants. Propolis has been reported to have immunomodulatory activity. We hypothesized that propolis would be able to reduce the disease severity of rheumatoid arthritis. We evaluated the effect of Brazilian propolis ethanolic extract on the pathogenesis of collagen-induced arthritis (CIA) in mice. Mice fed propolis exhibited significant lower clinical arthritis scores than those fed the control diet. To investigate the mechanism of the effect of propolis on CIA mice, we examined interleukin-17 (IL-17) production in CIA mice fed propolis using an enzyme-linked immunospot assay and flow cytometric analysis. The numbers of IL-17-producing cells in the CIA mice fed propolis were significantly decreased. To determine direct influence of propolis on cytokine production, splenocytes were stimulated with phorbol myristate acetate in the presence of propolis extract in vitro. Concentration-dependent declines in IL-17 expression were observed by ELISA and real-time PCR methods. We further found that propolis significantly inhibited the differentiation of Th17 cells from murine splenocytes in a concentration-dependent manner. Taken together, our results may provide a new light on the potential mechanism of the immunosuppressive and anti-inflammatory effects of propolis.

Tanaka M, Okamoto Y, Fukui T, Masuzawa T
Inflammopharmacology Feb 2012
PMID: 21861090


IL-17 is implicated in osteoporosis.

Zinc-Carnosine or Zinc Reduce IL-6 in Mouse Osteoblast-Like Cells

Abstract

Zinc suppresses IL-6 synthesis by prostaglandin F2alpha in osteoblasts: inhibition of phospholipase C and phospholipase D.

We previously reported that prostaglandin F2alpha (PGF2alpha) induces phosphoinositide hydrolysis by phospholipase C and phosphatidylcholine hydrolysis by phospholipase D through heterotrimeric GTP-binding protein, resulting in the activation of protein kinase C (PKC) in osteoblast-like MC3T3-E1 cells and that PGF2alpha stimulates the synthesis of interleukin-6 (IL-6) via PKC-dependent p44/p42 mitogen-activated protein (MAP) kinase activation. In the present study, we investigated whether zinc affects the PGF2alpha-induced IL-6 synthesis in these cells. Zinc complex of l-carnosine (l-CAZ) dose-dependently suppressed the PGF2alpha-stimulated IL-6 synthesis. In addition, zinc alone reduced the IL-6 synthesis. L-CAZ suppressed the PGF2alpha-induced p44/p42 MAP kinase phosphorylation. However, the p44/p42 MAP kinase phosphorylation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), a direct activator of PKC, or NaF, a direct activator of GTP-binding protein, was not affected by l-CAZ. l-CAZ reduced the PGF2alpha-stimulated formation of inositol phosphates and choline. However, l-CAZ did not affect the formation of inositol phosphates or choline induced by NaF. These results strongly suggest that zinc reduces PGF2alpha-induced IL-6 synthesis via suppression of phosphoinositide-hydrolyzing phospholipase C and phosphatidylcholine-hydrolyzing phospholipase D in osteoblasts.

Hatakeyama D, Kozawa O, Otsuka T, Shibata T…
J. Cell. Biochem. 2002
PMID: 11968002


Osteoblasts secrete IL-6 to stimulate osteoclast formation. Reducing IL-6 should help reduce resorption.

Magnesium in Bone is Higher When Taken More Frequently in Rats

Abstract

The frequency of magnesium consumption directly influences its serum concentration and the amount of elutable bone magnesium in rats.

We investigated the influence of Mg feeding frequency on the variation in serum Mg concentration and tissue Mg levels in Mg-deficient rats. Sprague-Dawley rats, which had been fed a Mg-deficient diet for 14 d, were divided into 3 groups that were kept on 3 diets differing in their Mg content. The rats were fed 0.5-fold (Mg250 group), 1-fold (Mg500 group), or 1.5-fold (Mg750 group) the amounts of recommended Mg in their standard AIN-93G diet (Mg: 478 mg/kg diet) during the recovery period (12 d). The Mg500 and Mg750 groups were intermittently fed (Mg500, every 2 d; Mg750, every 3 d) so that their total intake of Mg during the recovery period could equal the Mg intake of the Mg250 group. The serum Mg concentrations increased in the 3 groups after feeding with a Mg-containing diet. However, serum Mg levels were only maintained within the normal range in the Mg250 group. After feeding on the Mg-deficient diet, in the intermittently fed groups, serum Mg concentrations decreased. Urinary Mg excretion was higher and Mg retention was lower in the Mg500 and Mg750 groups than in the Mg250 group. Moreover, bone Mg, especially elutable bone Mg, was lower in the Mg500 and Mg750 groups than in the Mg250 group. The elutable fraction of bone Mg correlated to the coefficient of variation of serum Mg concentration. In conclusion, for the maintenance of serum Mg concentration, it is important to increase the amount of elutable bone Mg by frequent Mg consumption.

Nakaya Y, Uehara M, Katsumata S, Suzuki K…
Magnes Res Mar 2010
PMID: 20228011 | Free Full Text


Note the rats that ate 250mg/kg Magnesium had higher bone Magnesium than the rats fed just as much Magnesium but less often, every 2 or 3 days.

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.

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

MK-7 at 360mcg for a Year Does Not Benefit Postmenopausal Norwegian Women

Abstract

Vitamin K2 supplementation does not influence bone loss in early menopausal women: a randomised double-blind placebo-controlled trial.

Vitamin K2 may preserve bone strength and reduce fracture risk. In this randomised double-blind placebo-controlled trial among healthy postmenopausal Norwegian women, 1 year supplementation of vitamin K2 in the form of Natto capsules had no effect on bone loss rates. Japanese studies indicate that vitamin K2 (menaquinone-7 (MK-7)) intake may preserve bone strength, but this has not been documented in Europeans. The aim of this study was to assess the effect of MK-7 on bone mineral density (BMD) changes in postmenopausal Norwegian women.
Three hundred thirty-four healthy women between 50 and 60 years, 1-5 years after menopause, were recruited to a randomised double-blind placebo-controlled trial. The participants were randomly assigned into two groups, one receiving 360 microg MK-7 in the form of Natto capsules and the other the same amount of identical-looking placebo capsules containing olive oil. BMD was measured at total hip, femoral neck, lumbar spine and total body at baseline and 12 months together with serum levels of bone-specific alkaline phosphatase, Crosslaps, total osteocalcin (N-mid OC), carboxylated (cOC) and under-carboxylated osteocalcin (ucOC).
After 12 months, there were no statistical differences in bone loss rates between the groups at the total hip or any other measurement site. Serum levels of cOC increased and ucOC decreased in the treatment versus the placebo group (p < 0.001).
MK-7 taken as Natto over 1 year reduced serum levels of ucOC but did not influence bone loss rates in early menopausal women.

Emaus N, Gjesdal CG, Almås B, Christensen M…
Osteoporos Int Oct 2010
PMID: 19937427


360mcg is a fairly high dose, and they took it for a good long time. This is very disappointing  for MK-7.

Nutrients Correlated With Bone Density

Abstract

[Validation of questionnaires for the study of food habits and bone mass].

The loss of bone mass and density is influenced by nutritional factors that act on the bone mass peak, age-related bone loss and muscle strength. The objective of the present study was to validate a food frequency questionnaire applied to estimate the relationship between food habits and bone mineral density (BMD) in a healthy adult population.
The results of the food frequency questionnaire were compared with 24-hr recall findings. Calcaneus BMD was measured by densitometry.
The validity of the questionnaire was demonstrated, with Spearman correlation coefficients of 0.014 to 0.467. The Bland-Altman test also found no differences in study variables between the two methods. Correlation analysis showed that the BMD was significantly associated with the intake of vitamin D, vitamin A, vitamin B12, folate, thiamine and iron. Total fat consumption was not associated with BMD but the intake of monounsaturated fatty acids, EPA, DHA and cholesterol showed a significant correlation.
The questionnaire evaluates the consumption of energy and nutrients with adequate validity. Its application revealed the importance for bone health of a diet rich in B-group vitamins, vitamin D, calcium, iron, monounsaturated fatty acids and n-3.

Rivas A, Romero A, Mariscal M, Monteagudo C…
Nutr Hosp
PMID: 19893861 | Free Full Text | Full Text English Translation


The full text has a very interesting chart with a list of nutrients and their correlation with bone density.