Category Archives: Phytoestrogens

Review: Phytochemicals for Bone Osteoporosis

Abstract

Regulatory mechanism of food factors in bone metabolism and prevention of osteoporosis.

Aging induces a decrease in bone mass, and osteoporosis with its accompanying decrease in bone mass is widely recognized as a major public health problem. Bone loss with increasing age may be due to decreased bone formation and increased bone resorption. Pharmacologic and nutritional factors may prevent bone loss with aging, although chemical compounds in food and plants which act on bone metabolism are poorly understood. We have found that isoflavones (including genistein and daidzein), which are contained in soybeans, have a stimulatory effect on osteoblastic bone formation and an inhibitory effect on osteoclastic bone resorption, thereby increasing bone mass. Menaquinone-7, an analogue of vitamin K(2) which is abundant in fermented soybeans, has been demonstrated to stimulate osteoblastic bone formation and to inhibit osteoclastic bone resorption. Of various carotenoids, beta-cryptoxanthin, which is abundant in Satsuma mandarin (Citrus unchiu MARC), has a stimulatory effect on osteoblastic bone formation and an inhibitory effect on osteoclastic bone resorption. The supplementation of these factors has a preventive effect on bone loss induced by ovariectomy in rats, which are an animal model of osteoporosis, and their intake has been shown to have a stimulatory effect on bone mass in humans. Factors with an anabolic effect on bone metabolism were found in extracts obtained from wasabi leafstalk (Wasabi japonica MATSUM), the marine alga Sargassum horneri, and bee pollen Cistus ladaniferus. Phytocomponent p-hydroxycinnamic acid was also found to have an anabolic effect on bone metabolism. Food chemical factors thus play a role in bone health and may be important in the prevention of bone loss with increasing age.

Yamaguchi M
Yakugaku Zasshi Nov 2006
PMID: 17077614 | Free Full Text

Palash Prevents Bone Loss and Stimulates Formation in Ovariectomized Rats

Abstract

Total extract and standardized fraction from the stem bark of Butea monosperma have osteoprotective action: evidence for the nonestrogenic osteogenic effect of the standardized fraction.

The aim of this study was to determine the skeletal effects of Butea total extract (BTE) and its acetone soluble fraction (ASF) from Butea monosperma, which is rich in methoxyisoflavones, in ovariectomized (OVx) rats, a model for postmenopausal bone loss.
BTE (1.0 g kg d) and ASF (100 mg kg d) were given orally for 12 weeks to adult OVx rats. The sham-operated and ovariectomy + vehicle groups served as controls. Bone mineral density, osteoid formation (mineral apposition rate and bone formation rate), bone microarchitecture, and bone turnover/resorption markers were studied. Phytoestrogens in rats given BTE and ASF were analyzed by high-performance liquid chromatography. One-way analysis of variance was used to test significance of effects.
OVx rats treated with either BTE or ASF exhibited increased bone mineral density in trabecular bones and improved trabecular microarchitecture compared with the ovariectomy + vehicle group. ASF treatment was more efficient than BTE treatment in maintaining trabecular microarchitecture. Serum osteocalcin and urinary type 1 collagen levels in OVx rats treated with either BTE or ASF were significantly lower than those of the ovariectomy + vehicle group. ASF treatment led to increased mineral apposition rate and bone formation rate compared with ovariectomy + vehicle, whereas BTE had no such effect. In the uterotropic assay, BTE was mildly estrogenic in adult OVx rats. In immature rats, BTE exhibited both estrogenicity and antiestrogenicity. ASF had neither uterine estrogenicity nor antiestrogenicity. Analysis of phytoestrogens revealed significant enrichment of cladrin, isoformononetin, and medicarpin in ASF over BTE.
Derived from B monosperma, ASF at a 10-fold lower dose than that of BTE was effective in preventing OVx-induced bone loss and stimulated new-bone formation.

Pandey R, Gautam AK, Bhargavan B, Trivedi R…
Menopause
PMID: 20395887

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

Isoflavones More Effective Than Pure Genistein in Ovariectomized Rats

Abstract

Comparison of the bone protective effects of an isoflavone-rich diet with dietary and subcutaneous administrations of genistein in ovariectomized rats.

Administration of the isoflavone genistein (GEN) has been described to result in bone protection but also to induce uterotrophic responses. To compare bone protective effects of GEN with an isoflavone-rich diet (IRD) and to further elucidate molecular mechanisms involved in bone-protection, ovariectomized rats (OVX) received either a diet low in isoflavone content (IDD) enriched with GEN (42 mg kg(-1)b.wtd(-1)) (GEN(d)), an IRD (14 mg kg(-1)b.wtd(-1) GEN, 14 mg kg(-1)b.wtd(-1) daidzein) or were treated subcutaneously (s.c.) with GEN (10 mg kg(-1)b.wtd(-1)) (GEN(sc)) for 12 weeks. Intact (SHAM), vehicle treated OVX animals and those substituted with 17beta-estradiol (2microg kg(-1)b.wtd(-1)) (E(2)), served as controls. OVX-induced bone loss could be antagonized in E(2), GEN(sc), GEN(d) and IRD groups. Uterine wet weight (UWW) was only stimulated in E(2) and GEN(sc) animals. Serum biomarkers of bone-formation (osteocalcin, osteopontin) and bone-resorption (telopeptides of collagen type I, pyridinoline cross-links) were elevated in OVX compared to SHAM and E(2) animals. Feeding IRD stimulated bone-formation and inhibited bone-resorption, whereas s.c. or dietary administration of GEN only resulted in a stimulation of bone-formation. The results of the present study indicate that in contrast to s.c. administration, dietary intake of GEN resulted in bone protection without stimulation of UWW. Dietary intake of isoflavones by an IRD also did not result in a stimulation of UWW, yet IRD appeared to be more effective in bone protection than administration of pure GEN.

Hertrampf T, Schleipen B, Offermanns C, Velders M…
Toxicol. Lett. Feb 2009
PMID: 19063953

Review: Isoflavone Optimal Intake is 50-90mg

Abstract

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.

Messina M
Womens Health (Lond Engl) Jul 2008
PMID: 19072500