Monthly Archives: September 2013

Review: Protein + Calcium – May 2003

Abstract

Calcium and protein in bone health.

Dietary protein has several opposing effects on Ca balance and its net effect on bone is not well established. It has long been recognized that increasing protein intake increases urinary Ca excretion. More recently, it has been observed that increasing dietary protein raises the circulating level of insulin-like growth factor-1, a growth factor that promotes osteoblast formation and bone growth. Other effects of protein on the Ca economy have been suggested in some studies, but they are less well established. Several studies have examined associations between protein intake and bone loss and fracture rates. In the original Framingham cohort subjects with lower total and animal protein intakes had greater rates of bone loss from the femoral neck and spine than subjects consuming more protein. In another study higher total (and animal) protein intakes were associated with a reduced incidence of hip fractures in post-menopausal women. In contrast, a high animal:plant protein intake has been associated with greater bone loss from the femoral neck and a greater risk of hip fracture in older women. Higher total and higher animal protein intakes have also been associated with increased risk of forearm fracture in younger post-menopausal women. In a recent study it was found that increasing dietary protein was associated with a favourable (positive) change in bone mineral density of the femoral neck and total body in subjects taking supplemental calcium citrate malate with vitamin D, but not in those taking placebo. The possibility that Ca intake may influence the impact of dietary protein on the skeleton warrants further investigation.

Dawson-Hughes B
Proc Nutr Soc May 2003
PMID: 14506898

Review: Protein – March 2003

Abstract

Protein and bone health: literature review and counselling implications.

For decades, public health promotion campaigns on bone health have emphasized the importance of adequate calcium and vitamin D intakes, as well as weight-bearing physical activity. However, no obvious consensus has emerged on the role of dietary protein. To identify what agreement does exist in the literature, in this article we review the theoretical basis for protein’s role in bone health, assess some recent cross-sectional and prospective studies, and generate recommendations for practice. There is general agreement in the literature that higher protein intake increases urinary calcium loss; the body compensates for this loss by increasing calcium absorption in the gut, providing that calcium intake is sufficient. A possible explanation for calcium loss, the “acid-ash” hypothesis, is discussed, and suggestions are made about food choices that may counter the calciuric effect of protein. A survey of cross-sectional and prospective studies shows equivocal results, with confounding variables complicating the analysis. Both deficient and excessive protein intakes have been shown to affect bone health negatively, although lower and upper thresholds have not been determined. Practical advice on achieving bone health is given, with an emphasis on the use of Canada’s Food Guide to Healthy Eating in setting dietary goals.

Cloutier GR, Barr SI
Can J Diet Pract Res 2003
PMID: 12631403

Review: Protein + Calcium – March 2003

Abstract

Interaction of dietary calcium and protein in bone health in humans.

Protein has both positive and negative effects on calcium balance, and the net effect of dietary protein on bone mass and fracture risk may be dependent on the dietary calcium intake. In addition to providing substrate for bone matrix, dietary protein stimulates the production of insulin-like growth factor-1 (IGF-1), a factor that promotes osteoblast-mediated bone formation. Protein also increases urinary calcium losses, by several proposed mechanisms. Increasing calcium intake may offset the negative impact of dietary protein on urinary calcium losses, allowing the favorable effect of protein on the IGF-1 axis to dominate. Several, although not all, studies are either compatible with or support this hypothesis. Protein supplements significantly reduced bone loss in elderly hip-fracture patients in a study in which both the protein and control groups received supplemental calcium. In an observational study, total protein intake was positively associated with favorable 3-y changes in femoral neck and total body bone mineral density in volunteers who received supplemental calcium citrate malate and vitamin D, but not in volunteers taking placebos. In conclusion, an adequate calcium intake may help promote a favorable effect of dietary protein on the skeleton in older individuals.

Dawson-Hughes B
J. Nutr. Mar 2003
PMID: 12612168 | Free Full Text

Onion Decreases Osteopenia in Rats

Abstract

Onion decreases the ovariectomy-induced osteopenia in young adult rats.

It has been suggested that fruit and vegetable consumption are associated with good bone health. Onion, in particular, has been verified in its efficacy in bone resorption activity. In this study, we further investigated the effects of an onion-containing diet on ovariectomy-induced bone loss using methods of serum marker assay, histomorphometric analysis and biomechanical tests. Sixty-four female Wistar rats (14-week-old) with sham operations or ovariectomy were assigned to 6 groups: CON, sham-operated control group; OVX, ovariectomized group; ALN, ovariectomized rats treated with alendronate (1 mg/kg/day, p.o.); and 3% ON, 7% ON and 14% ON, ovariectomized rats fed with diets containing 3%, 7% and 14% (wt/wt) onion powder, respectively. Animals were sacrificed after a six-week treatment course. In the serum marker assay, alendronate and all three onion-enriched diets significantly decreased serum calcium level (p<0.05). Both 14% ON group and the ALN group even showed similarly lower level of serum osteocalcin (p<0.05), suggesting a down-regulation of bone turnover. The histomorphometric analysis showed that ovariectomy markedly decrease bone trabeculae. The ALN and 14% ON rats were 80% and 46% higher, respectively, in BV/TV than the OVX rats (p<0.05), and the rats fed with onion-enriched food showed a lesser ovariectomy-induced bone loss in a dose-dependent manner. Additionally, both ALN and 14% ON groups had significantly more trabecular number, less separated trabeculae, and fewer osteoclasts (p<0.05), but the protective efficacy from the 14% onion-enriched diet was slightly inferior to that of alendronate. Ovariectomy also significantly decreased tissue weight and biomechanical strength in the OVX group (p<0.05). The ALN and 14% ON groups equivalently showed a lesser decrease in tissue weight, though the difference was not significant. On the other hand, both the ALN and 14% ON groups represented similar biomaterial properties of femurs, and both reduced the ovariectomy-induced decrease in bending load and bending energy (p<0.05). The present study further verified that an onion-enriched diet could counteract ovariectomy-induced bone loss and deterioration of biomechanical properties.

Huang TH, Mühlbauer RC, Tang CH, Chen HI…
Bone Jun 2008
PMID: 18387868

Genistein Increases Bone Density in Rats, Cooked Soybeans and Stachyose Don’t

Abstract

Influence of a low dose of dietary soybean on bone properties and mineral status in young rats.

The aim of this study was to evaluate effects of dietary supplementation with genistein, daidzein stachyose, and raw or cooked soybean on mineral content, optical density, and mechanical properties of bones in growing rats. The experiment was performed on 70 male young Wistar rats (4 weeks old at the start of the experiment) divided into seven groups. Genistein, daidzein, or stachyose were administered by gavage. Raw or cooked soybean was added directly to the diet (1%) The experiment lasted 28 days. Femurs were removed postmortem and kept until analysis at -20°C. Mineral content in bones was determined by atomic absorption flame spectrometry, and inductively coupled plasma atomic emission spectrometry. Optical density was analyzed with a KODAK 1D 3.5 system. Mechanical properties were tested using INSTRON 4301 equipment. Genistein increased mineral content in bones of growing rats. Biological action of genistein and daidzein on the mineralization of bone tissues in growing rats was different. Addition of stachyose (1.9 mg/day/rat) did not affect bone tissues, nor did the addition of raw or cooked soybean. None of the studied biologically active substances: genistein (0.26 mg/day/rat), daidzein (0.104 mg/day/rat), stachyose (1.9 mg/day/rat), or soybean had an effect on bone optical density.

Piastowska-Ciesielska AW, Gralak MA
Biofactors
PMID: 20806285

Review: Vitamin D + Isoflavones may be Synergistic

Abstract

Vitamin D interactions with soy isoflavones on bone after menopause: a review.

Vitamin D is known to increase Ca absorption in adults. However, the threshold vitamin D status to benefit Ca absorption is lower than the target vitamin D status for higher bone mineral density and lower fracture risk, pointing to another pathway for vitamin D to benefit bone. One possibility is by affecting osteoblast and osteoclasts directly. Vitamin D-related bone metabolism may also be affected by soy isoflavones, which selectively bind to the estrogen receptor β and may reduce bone loss in postmenopausal women. We discuss a possible synergistic effect of soy isoflavones and vitamin D on bone by affecting osteoblast and osteoclast formation and activity in postmenopausal women.

Park CY, Weaver CM
Nutrients Nov 2012
PMID: 23201836 | Free Full Text

Review: Isoflavones Benefits May be Due to Equol

Abstract

Isoflavone metabolism and bone-sparing effects of daidzein-metabolites.

Several dietary phytochemicals exhibit anti-oxidative, anti-inflammatory and anti-osteoporotic activities relevant to prevention of chronic diseases, including lifestyle-related diseases. Soybean isoflavones are similar in structure to estrogen and have received considerable attention as potential alternatives to hormone replacement therapy. Daidzein, a major isoflavone found in soybean, is metabolized to equol by intestinal microflora; this metabolite exhibits stronger estrogenic activity than daidzein. Recent studies suggest that the clinical effectiveness of isoflavones might be due to their ability to produce equol in the gut. This review focused on the metabolic pathway of equol and possible bioactivities of equol and O-desmethylangolensin, another metabolite of daidzein, with regard to bone metabolism and the status of intestinal microflora. Furthermore, we considered risk-benefit analyses of isoflavones and their metabolites.

Uehara M
J Clin Biochem Nutr May 2013
PMID: 23704808 | Free Full Text

Isoflavones + Calcium Better Than Isoflavones or Calcium in Ovariectomized Rats

Abstract

Isoflavones with supplemental calcium provide greater protection against the loss of bone mass and strength after ovariectomy compared to isoflavones alone.

Although hormone replacement therapy (HRT) and calcium (Ca) supplementation preserve bone mass more when combined, there is a growing concern over the safety of HRT that necessitates thorough investigation of effective, alternative treatments for bone loss. While plant-derived estrogen-like compounds such as isoflavones preserve bone, it is not known whether isoflavones and Ca supplementation attenuate losses in bone mass and strength to a greater extent when combined. This study compared the effects of an isoflavone extract + high Ca to isoflavone extract or high Ca alone on preservation of bone mineral density (BMD) and biomechanical strength in ovariectomized (ovx) rats. Rats were sham-operated (n = 10) or ovx (n = 40). Shams were fed a 0.2% Ca diet. Ovx rats were randomized to a 0.2% Ca diet alone (OVX) or with isoflavone extract (IE; 1.6 g/kg diet) or to a high Ca diet (Ca; 2.5%) alone or a high Ca diet with the isoflavone extract (IE + Ca) for 8 weeks. BMD of femur and lumbar spine were measured by dual-energy X-ray absorptiometry. The biomechanical strength of femurs and individual vertebra was measured by three-point bending and compression testing, respectively. The average food intake was lowest (P < 0.05) among sham and IE groups and greatest (P < 0.05) among the OVX group. Final body weight was lowest (P < 0.05) among shams and highest (P < 0.05) among the OVX group while IE + Ca were lighter (P < 0.05) than all ovx groups. Femur and vertebra BMD was greater (P < 0.05) among IE + Ca and sham rats compared to IE, Ca, or OVX rats. Although there were differences in femur BMD among groups, biomechanical properties at the femur midpoint did not differ among groups, possibly due to the lack of cortical bone loss at this site. Conversely, vertebra biomechanical strength was greater (P < 0.05) among IE + Ca and Ca alone groups compared to IE alone. Uterine weight was higher (P < 0.05) among shams than OVX and IE with no difference among shams, Ca, or IE + Ca rats, suggesting that the isoflavones did not have an uterotrophic effect. In conclusion, isoflavones combined with high Ca are more protective against the loss of femur and vertebra BMD than isoflavones or high Ca diet alone.

Breitman PL, Fonseca D, Cheung AM, Ward WE
Bone Oct 2003
PMID: 14555264

Also, it’s interesting that Calcium alone was superior to Isoflavones alone.

Daidzein Alone Did Not Preserve Trabecular Bone in Ovariectomized Mice

Abstract

Daidzein together with high calcium preserve bone mass and biomechanical strength at multiple sites in ovariectomized mice.

As the prevalence of osteoporosis is increasing, and the adverse effects of hormone replacement therapy are evident, women are searching for natural alternatives such as soy isoflavones to help prevent postmenopausal osteoporosis. Daidzein is one of the most abundant isoflavones present in soy and it is unique as it can be further metabolized to equol, a compound with greater estrogenic activity than other isoflavones. The objective of this study was to determine the effects of purified daidzein in combination with high calcium (Ca) on preserving femur and lumbar vertebrae (LV1-LV4) bone mineral density (BMD) and biomechanical bone strength at three different sites (femur midpoint, femur neck and LV3) in ovariectomized mice. Sham (SH) mice (n = 12) received control diet (AIN93G) containing 2 g Ca/kg diet and ovariectomized mice were randomized to 1 of 6 groups (n = 12/group): OVX (2 g Ca/kg diet), HCa (25 g Ca/kg diet), HD (2 g Ca + 200 mg daidzein/kg diet), HDCa (25 g Ca + 200 mg daidzein/kg diet), LD (2 g Ca + 100 mg daidzein/kg diet) or LDCa (25 g Ca + 100 mg daidzein/kg diet) for 12 weeks. HDCa preserved femur and vertebrae BMD and biomechanical bone strength (at all three sites) compared to the OVX group, however, only femur yield load (at midpoint) was preserved to a level that was greater (P < 0.05) than HCa alone. Mice fed HD diet had greater (P < 0.05) femur BMD than OVX group, however, daidzein alone (HD) did not appear to preserve trabecular bone (i.e., vertebrae BMD and vertebra peak load). All mice fed daidzein produced equol and there were no uterotrophic effects of daidzein at either dose. Both daidzein and Ca attenuated the increase in serum IL-1beta observed in the OVX group. The results from this study suggest that the combination of daidzein and high Ca favorably affect cortical and trabecular bone as indicated by femur and lumbar vertebrae BMD and biomechanical strength but much of this effect is mediated by the high Ca diet. Further investigation is required to determine optimal dietary levels of daidzein and Ca with the long-term goal of developing a dietary strategy to prevent postmenopausal osteoporosis and related fragility fractures.

Fonseca D, Ward WE
Bone Aug 2004
PMID: 15268901

Genistein Increases Bone Density While Being an Anti-Estrogen Elsewhere in Ovariectomized Mice

Abstract

Estrogenic agonism and antagonism of the soy isoflavone genistein in uterus, bone and lymphopoiesis in mice.

The isoflavone genistein (Gen) is a naturally occurring phytoestrogen found in high concentrations in soy. The biological effects of Gen have been extensively studied. The immunomodulating properties of Gen are, however, less well investigated and the results are contradictory. Our aim was to study possible estrogen agonistic and antagonistic properties of Gen in uterus, bone, lymphopoiesis and B-cell function by comparing effects in castrated and intact female mice, respectively. Oophorectomized (OVX) and sham-operated mice were treated with s.c. doses of 17beta-estradiol (E2) (0.16 mg/kg), Gen (50 mg/kg), or vehicle (olive oil) as control. Effects on bone mineral density (BMD) were studied using peripheral quantitative computerized tomography, uterine and thymus weights were examined, lymphopoiesis in thymus and bone marrow was analyzed using flow cytometry, and the frequency of immunoglobulin-producing B cells in bone marrow and spleen was studied using an ELISPOT assay. Gen was clearly antagonizing endogenous estrogen in sham-operated female mice as shown by inhibiting the uterine weight and by increasing the frequency of B lymphopoietic cells in bone marrow. The only agonistic effect of Gen was shown by increased BMD in OVX mice. Our results are discussed in the context of estrogen receptor biology.

Erlandsson MC, Islander U, Moverare S, Ohlsson C…
APMIS May 2005
PMID: 16011657