Combined effect of soy isoflavones and vitamin D3 on bone loss in ovariectomized rats.
Several studies have shown that soy isoflavones have estrogen-like activities and might constitute an alternative to hormone replacement treatment. The present study investigated the effects of soy isoflavones alone and combined with vitamin D3 on prevention of bone loss.
Sprague-Dawley rats were sham-operated (n = 8) or ovariectomized (OVX; n = 40), and then the OVX rats were randomly assigned to five groups that were untreated or treated for 14 wk with vitamin D3, 17β-estradiol, soy isoflavone extract (SIE), or vitamin D3 plus SIE. The effects of the isoflavones and 1α,25(OH)(2)D(3) on cultured osteoblasts and osteoclasts also were investigated.
In OVX rats, the bone mineral density and trabecular bone volume loss were improved by 17β-estradiol, SIE, or SIE plus vitamin D3 treatment. SIE treatment was more effective than vitamin D3 or 17β-estradiol in inhibiting increases in serum tumor necrosis factor-α levels and osteoblast osteoprotegerin expression. SIE plus vitamin D3 was more effective in increasing osterix expression than each alone. Bone cell cultures showed that the isoflavones induced preosteoblasts to differentiate into osteoblasts and increased osteoblast mineralization. Isoflavones inhibited preosteoclasts and osteoclast proliferation and decreased osteoclast resorption. The combination of isoflavones plus 1α,25(OH)(2)D(3) showed additive effects on the increase in cell proliferation of cultured preosteoblasts. Treatment with soy isoflavones might be an alternative to hormone replacement therapy in decreasing bone loss from postmenopausal estrogen deficiency. In addition, there are further effects on increasing transcription factor osterix expression and preosteoblast proliferation when these were combined with vitamin D3.
Chang KL, Hu YC, Hsieh BS, Cheng HL…
Nutrition Jan 2013 PMID: 22858193
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.
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
Investigating the optimal soy protein and isoflavone intakes for women: a perspective.
Traditional soyfoods have been consumed for centuries throughout much of East Asia and, recently, these foods have also become popular in the West. Soyfoods and specific soybean components, such as the protein and isoflavones, have attracted attention for their possible health benefits. Isoflavones are classified as phytoestrogens and have been postulated to be natural alternatives to hormone therapy for menopausal women. To provide guidance on optimal soy intake, this article evaluates Asian soy consumption and both clinical and Asian epidemiologic studies that examined the relationship between soy intake and a variety of health outcomes. On the basis of these data and the standard principles of dietary practice the author suggests that optimal soy protein and isoflavone intakes are 15-20 g/day and 50-90 mg/day, respectively. In addition, an intake of 25 g/day soy protein can be specifically used as the recommendation for cholesterol reduction.
Consumption of legumes improves certain bone markers in ovariectomized rats.
Soybeans are known to protect against osteoporosis, but other legumes frequently consumed in Asia have not been studied to learn if they have a similar protective effect. This study investigated the hypothesis that consumption of soybean, mung bean, cowpea, and adzuki bean has beneficial effects on bone biomarkers in ovariectomized rats. Female Sprague-Dawley rats were either sham operated (sham; n = 7) or surgically ovariectomized and then fed a regular AIN-93M diet (OVX; n = 7) or AIN-93M containing soybean (n = 7), mung bean (n = 7), cowpea (n = 7), or adzuki beans (n = 7) for 10 weeks. No bean consumption significantly altered the body, subcutaneous fat, or uterus weight; however, consumption significantly increased the serum calcium/phosphorous ratio and decreased urinary calcium excretion compared with those of the OVX group. Serum concentration of 17β-estradiol was significantly lower in the OVX group compared with that of the sham group and was lowest in the group fed OVX diet containing soybean. Serum osteocalcin concentration was significantly higher in all OVX rats given a diet with beans compared with the same diet without, but urinary deoxypyridinoline excretion was lowest in the group fed OVX diet containing cowpea. There were no significant differences in bone mineral density or bone mineral content of the right femur, tibia, or lumbar spine or in the trabecular bone volume of the tibia among the diet groups. In conclusion, the consumption of soybean, mung bean, cowpea, and adzuki bean in OVX rats improved osteocalcin, but only those fed cowpea showed decreased bone resorption biomarker, suggesting that cowpea may have the most protective effect on bone in OVX rats.
Modulation of soy isoflavones bioavailability and subsequent effects on bone health in ovariectomized rats: the case for equol.
Soy products are of particular interest because of their potential health benefits in a range of hormonal conditions, such as osteoporosis, due to their high content in phytoestrogens. Because equol, the main metabolite from soy isoflavones, is thought to be powerful, the present study was designated to evaluate the bone-sparing effects of equol by either providing the molecule through the diet or by eliciting its endogenous production by modulating intestinal microflora by short-chain fructooligosaccharides (sc-FOS) or live microbial (Lactobacillus casei) together with daidzein, its precursor.
A comparison with daidzein and genistein was also performed. Rats (3 months old) were ovariectomised (OVX) or sham-operated (SH). Ovariectomised rats were randomly assigned to six experimental diets for 3 months: a control diet (OVX), the control diet supplemented with either genistein (G), or daidzein (D), or equol (E) at the level of 10 microg/g body weight/d. The remaining OVX rats were given daidzein at the dose of 10 mug/g body weight/d, simultaneously with short-chain FOS (Actilight, Beghin-Meiji) (D+FOS) or Lactobacillus casei (Actimel, Danone) (D+L). The SH rats were given the same control diet as OVX.
Genistein, daidzein or equol exhibited a bone sparing effect. Indeed, total femoral bone mineral density (BMD) was significantly enhanced (compared to that of OVX rats), as was the metaphyseal compartment. Bone strength was improved by E consumption, but not by genistein or daidzein given alone. As far as the FOS diet is concerned, the addition of prebiotics significantly raised efficiency of the daidzein protective effect on both femoral BMD and mechanical properties. The effects of lactobacillus were similar, except that the increase in metaphyseal-BMD was not significant.
In conclusion, long-term equol consumption, like genistein and daidzein, in the ovariectomized rat, provides bone sparing effects. Adding indigestible sugars, such as FOS or live microbial as L. casei, in the diet significantly improves daidzein protective effects on the skeleton.
Mathey J, Mardon J, Fokialakis N, Puel C…
Osteoporos Int May 2007 PMID: 17333448
The effects of fructo-oligosaccharides in combination with soy protein on bone in osteopenic ovariectomized rats.
The intestinal microflora is important in rendering soy isoflavones bioavailable by facilitating their conversion to equol. Hence, substances that can modulate the intestinal microflora could affect the bioavailability of isoflavones. In this study, we examined the effects of fructo-oligosaccharides (FOS), a prebiotic, on enhancing the effects of soy isoflavones on bone in ovariectomized osteopenic female rats.
Sixty-three 9-month-old female Sprague-Dawley rats were either sham-operated (Sham; one group) or ovariectomized (Ovx; four groups) and were fed a control diet for 3 months to induce bone loss. After bone loss was confirmed via dual-energy x-ray absorptiometry, rats were placed on dietary treatment for 4 months. The Sham and one Ovx group received a control diet, and the remaining Ovx groups received either a soy protein-based diet (Soy), a FOS-supplemented diet (FOS), or a soy protein-based and FOS-supplemented diet (Soy+FOS). Before the termination of the study, whole-body bone mineral density (BMD) and bone mineral content (BMC) were assessed under anesthesia. Immediately after euthanasia, bone specimens were collected for the assessments of BMD, BMC, and biomechanical and microarchitectural properties.
Whole-body BMD values were significantly higher in FOS and Soy+FOS groups compared with Ovx controls. The tibial BMC increased by 10%, 6%, and 4% in Soy, FOS, and Soy+FOS groups, respectively, compared to the Ovx control group. FOS and FOS+Soy treatments had the most pronounced effects in enhancing lumbar BMC and BMD. The FOS+Soy combination effectively improved tibial microarchitectural properties by enhancing trabecular number and lowering trabecular separation compared with Ovx controls. The effects of dietary treatments on lumbar microarchitectural properties were minimal and biomechanical properties of the femur were not affected by any of the dietary treatments.
Our findings suggest that, although incorporation of either soy or FOS in the diet of Ovx rats can improve BMD of the whole body, tibiae, and lumbar vertebrae, their combination had no any additive effects. However, in terms of microarchitecture, the combination of soy and FOS had a greater effect in reversing the loss of certain microarchitectural parameters such as tibial trabecular number, separation, and thickness.
Addition of fructooligosaccharides and dried plum to soy-based diets reverses bone loss in the ovariectomized rat.
Dietary bioactive components that play a role in improving skeletal health have received considerable attention in complementary and alternative medicine practices as a result of their increased efficacy to combat chronic diseases. The objectives of this study were to evaluate the additive or synergistic effects of dried plum and fructooligosaccharides (FOS) and to determine whether dried plum and FOS or their combination in a soy protein-based diet can restore bone mass in ovarian hormone deficient rats. For this purpose, 72 3-month-old female Sprague-Dawley rats were divided into six groups (n = 12) and either ovariectomized (Ovx, five groups) or sham-operated (sham, one group). The rats were maintained on a semipurified standard diet for 45 days after surgery to establish bone loss. Thereafter, the rats were placed on one of the following dietary treatments for 60 days: casein-based diet (Sham and Ovx), soy-based diet (Ovx + soy) or soy-based diet with dried plum (Ovx + soy + plum), FOS (Ovx + soy + FOS) and combination of dried plum and FOS (Ovx + soy + plum + FOS). Soy protein in combination with the test compounds significantly improved whole-body bone mineral density (BMD). All test compounds in combination with soy protein significantly increased femoral BMD but the combination of soy protein, dried plum and FOS had the most pronounced effect in increasing lumbar BMD. Similarly, all of the test compounds increased ultimate load, indicating improved biomechanical properties. The positive effects of these test compounds on bone may be due to their ability to modulate bone resorption and formation, as shown by suppressed urinary deoxypyridinoline excretion and enhanced alkaline phosphatase activity.