Assessment of enhancement of peak bone gain by isoflavone enriched standardized soy extract in female rats (original) (raw)
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The American Journal of Clinical Nutrition
Soy protein, a rich source of isoflavones, fed immediately after an ovariectomy prevents bone loss in rats. Reports of the effectiveness of natural and synthetic isoflavones in preventing or treating osteoporosis led us to examine the effect of soy protein in reversing established bone loss. Seventytwo 95-d-old female Sprague-Dawley rats were assigned to 6 groups. The rats were either sham operated (SHAM; 2 groups) or ovariectomized (OVX; 4 groups) and then fed a casein-based, semipurified diet. Thirty-five days after surgery, 1 SHAM and 1 OVX group were killed to examine the occurrence of bone loss. Thereafter, the other SHAM and 1 OVX groups continued to receive the casein-based diet. Whereas the remaining 2 OVX groups received diets in which casein was replaced by soy protein with normal (OVX+SOY) or reduced (OVX+SOYϪ) isoflavone content for 65 days. The OVX control group had significantly lower femoral and fourth lumbar vertebral bone densities than the SHAM group. Femoral density of rats fed SOY or SOYϪ diets were not significantly different from SHAM or OVX controls. This suggests a slight reversal of cortical bone loss that may be partially due to higher femoral insulin-like growth factor I mRNA transcripts resulting from both the SOY and SOYϪ diets. The ovariectomy-induced increases in indexes of bone turnover were not ameliorated by either of the soy diets, suggesting that any positive effect of soy was achieved through enhanced bone formation rather than slowed bone resorption. Long-term consumption of soy or its isoflavones may be needed to produce small but continued increments in bone mass.
The American Journal of Clinical Nutrition
Our previous studies showed that a soy-protein diet prevents ovariectomy-induced bone loss. The purpose of this study was to determine whether isoflavones in soy protein are responsible for this bone-protective effect. Forty-eight 95-d-old Sprague-Dawley rats were divided into 4 groups: sham-operated fed a casein-based diet (SHAM), ovariectomized fed a caseinbased diet (OVX+CASEIN), ovariectomized fed soy protein with normal isoflavone content (OVX+SOY), and ovariectomized fed soy protein with reduced isoflavone content (OVX+SOYϪ). The OVX+SOY group had significantly greater femoral bone density (in g/cm 3 bone vol) than the OVX+CASEIN group, whereas OVX+SOYϪ was similar to OVX+CASEIN (x-± SD; SHAM, 1.522 ± 0.041; OVX+CASEIN, 1.449 ± 0.044; OVX+SOY, 1.497 ± 0.030; OVX+SOYϪ, 1.452 ± 0.030). Ovariectomy resulted in greater bone turnover as indicated by higher serum alkaline phosphatase activity, serum insulin-like growth factor I and insulin-like growth factor binding protein 3 concentrations, and urinary hydroxyproline. These increases were not affected by soy with either normal or reduced isoflavone content. Similarly, histomorphometry revealed a greater bone formation rate with ovariectomy, and this was not altered by the soy diets. The findings of this study suggest that isoflavones in soy protein are responsible for its bone-sparing effects. Further studies to evaluate the mechanism of action of isoflavones on bone are warranted.
The Journal of …, 2001
We assessed the dose-dependent effects of daily soybean isoflavone (IF) consumption in reversing bone loss in adult ovariectomized rats. On d 0, female Wistar rats (7 mo old; n ϭ 55) were either sham-operated (SH; n ϭ 14) or ovariectomized (n ϭ 41). On d 80, intermediate rats (SH: n ϭ 5; ovariectomized: n ϭ 5) were killed to confirm the ovariectomy-induced bone loss. The remaining ovariectomized rats were randomly assigned to one of four groups of nine rats each and fed soybean IF (mixed with a soy protein-free semipurified diet) at 0 (OVX), 20 (IF20), 40 (IF40) or 80 (IF80) mg/(kg body ⅐ d) for 84 d. Simultaneously, SH rats were fed the semipurified diet without any additional compound and killed on d 164, as were the other rats. As expected, both bone mineral density in the total femur and in its diaphyseal and metaphyseal subregions and cancellous bone area/measured surface in the distal femur metaphysis were lower in OVX than in SH rats (P Ͻ 0.05). OVX rats had higher plasma osteocalcin concentration and urinary deoxypyridinoline excretion than SH rats (P Ͻ 0.05). On d 164, osteocalcin and deoxypyridinoline concentrations were lower in IF40 or IF80 rats than in OVX rats (P Ͻ 0.05). Nevertheless, neither bone mineral density nor cancellous bone area was greater in IF-fed rats than in OVX rats. Therefore, in adult ovariectomized rats, daily soybean IF consumption decreased bone turnover but did not reverse established osteopenia. J. Nutr. 131: 723-728, 2001.
Osteoporosis International, 2007
Introduction 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. Methods 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 μg/g body weight/d. The remaining OVX rats were given daidzein at the dose of 10 μg/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. Results 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. Conclusion 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.
Nutrition Research, 2012
Soy with its isoflavones has been shown to positively influence bone mineral density in female ovariectomized rats; hence, we hypothesized a similar effect in orchidectomized (ORX) male rats. Forty male Sprague-Dawley rats, aged 95 days, were divided into 4 groups and were either sham operated (Sham) or ORX. The ORX groups were fed a soy proteinbased diet (SOY), an isoflavone-depleted soy protein diet (SOY−), or a casein based diet for 65 days after surgery. Orchidectomy increased the rate of bone turnover, resulting in reduced bone mineral density and bone mineral content by 3.5% and 14%, respectively, and compromised biomechanical properties. The mean femoral length of ORX animals was also significantly shorter than Sham animals, but ORX rats that were fed SOY diet did not experience this reduction in bone length, implicating a role for soy protein in bone growth (4.02 ± 0.02, 3.93 ± 0.01, 3.99 ± 0.02, 3.91 ± 0.01 for Sham, ORX, SOY, SOY−, respectively). The SOY and SOY− positively influenced the biomechanical properties of bone such as yield and ultimate force, the measures of bone elasticity, and plasticity. In terms of bone histomorphometry, the data indicate that SOY− tends to reduce ORX-induced increase in bone turnover as evidenced by suppressed bone formation rate/mineralized surface by about 9%. Overall, our results indicated that soy protein, regardless of its isoflavone content, was unable to prevent the ORX-induced femoral decrease in bone density and mineral content.
Menopause, 2005
Objective: The present study was conducted to determine the effects of dietary soy protein and isoflavones on bone and the reproductive tract in the absence of the ovary. Design: Three-month-old Sprague-Dawley rats (n = 56) were either sham-operated or ovariectomized and then fed diets containing casein or soy protein ± isoflavone extract for 12 weeks. The amounts of casein, soy protein, and extract (per kg diet) in each group were as follows: (1) Ovariectomy, 200 g of casein; (2) Ovariectomy+low soy, 100 g of casein + 100 g of soy protein; (3) Ovariectomy+high soy, 200 g of soy protein; (4) Ovariectomy+low extract, 200 g of casein + 17.2 g of extract; (5) Ovariectomy+high extract, 200 g of casein + 34.4 g of extract; (6) Ovary intact, 200 g of casein; (7) Ovariectomy+estradiol-17b, 200 g of casein. Diet consumption, body weight, uterine weight, urine deoxypyridinoline, and bone mineral density of the femur and lumbar vertebrae were measured. The femur rigidity was evaluated by histomorphometry. The reproductive tract (uterus, vagina, and cervix) was studied histologically. Results: The Ovariectomy group showed significant increases in body weight, diet consumption, and deoxypyridinoline, decreases in uterine weight and bone mineral density, and negative changes in histomorphometry compared with the Ovary intact group. Neither soy protein nor extract diets abrogated these alterations, except for the Ovariectomy+high extract group that showed statistically significant positive changes in histomorphometric parameters. There were no histological differences in the reproductive tract among Ovariectomy, Ovariectomy+soy, and Ovariectomy+extract groups. The estradiol-17b replacement abrogated ovariectomy-induced alterations. Conclusion: Dietary intake of isoflavones by sexually mature ovariectomized rats has a minimal beneficial effect on bone with no effect on the reproductive tract.
Animal studies have shown that soy isoflavones have an effect in preventing estrogen-related bone loss, but few data are available in humans, especially in the Asian populations. This double-blind, placebo-controlled, randomized trial examines the effects of soy isoflavones on bone loss in postmenopausal Chinese women, aged 48 -62 yr. Two hundred and three eligible subjects were randomly assigned to three treatment groups with daily doses of placebo (1 g starch; n ؍ 67), middose (0.5 g starch, 0.5 g soy extracts, and ϳ40 mg isoflavones; n ؍ 68), and high dose (1.0 g soy extracts and ϳ80 mg isoflavones; n ؍ 68). All were given 12.5 mmol (500 mg) calcium and 125 IU vitamin D 3 . Bone mineral density (BMD) and bone mineral content (BMC) of the whole body, spine, and hip were measured using dual energy x-ray absorptiometry at baseline and 1 yr post treatment. Both univariate and multivariate analyses showed that women in the high dose group had mild, but statistically significantly, higher favorable change rate in BMC at the total hip and trochanter (P < 0.05) compared with the placebo and mid-dose groups, even after further adjustments for the potential confounding factors. Further stratified analyses revealed that the positive effects of soy isoflavone supplementation were observed only among women with lower initial baseline BMC (median or less). In conclusion, soy isoflavones have a mild, but significant, independent effect on the maintenance of hip BMC in postmenopausal women with low initial bone mass. (J Clin Endocrinol Metab 88: 4740 -4747, 2003)