Shanil Juma

Bone-sparing effect of soy protein in ovarian hormone-deficient rats is related to its isoflavone content.

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 casein-based diet (OVX+CASEIN), ovariectomized fed soy protein with normal isoflavone content (OVX+SOY), and ovariectomized fed soy protein with reduced isoflavone content (OVX+SOY-). The OVX+SOY group had significantly greater femoral bone density (in g/cm3 bone vol) than the OVX+CASEIN group, whereas OVX+SOY- was similar to OVX+CASEIN (mean +/- SD; SHAM, 1.522 +/- 0.041; OVX+CASEIN, 1.449 +/- 0.044; OVX+SOY, 1.497 +/- 0.030; OVX+SOY-, 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.

Role of soy protein with normal or reduced isoflavone content in reversing bone loss induced by ovarian hormone deficiency in rats.

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. Seventy-two 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+SOY-) 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 SOY- 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 SOY- 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.

Whole flaxseed consumption lowers serum LDL-cholesterol and lipoprotein(a) concentrations in postmenopausal women

Abstract We conducted a double-blind cross-over study to compare the effects of whole flaxseed and sunflower seed, as part of the daily diet, on the lipid profile of postmenopausal women. During two 6-wk periods, thirty-eight mild, moderate, or severely (5.85–9.05 mmol/L) hypercholesterolemic postmenopausal women were randomly assigned to one of the two regimens: flaxseed or sunflower seed. The subjects were provided with 38 g of either treatment in the forms of breads and muffins. The first treatment period lasted six weeks and was followed by a two-wk washout phase. After the washout phase, subjects switched regimens and treatments continued for another 6 weeks. Blood samples were collected at baseline, 6, 8, and 14th wk of the study periods. Significant ( p p p

Vitamin E improves bone quality in the aged but not in young adult male mice

It is generally viewed that with advancing age, humans and other animals including mice experience a gradual decline in the rate of bone formation. This, in part, may be due to the rise in oxygen-derived free radical formation. Vitamin E, a strong antioxidant, functions as a free radical scavenger that potentially can suppress bone resorption while stimulating bone formation. Although the effects of vitamin E on immune functions are well documented, there is a paucity of information on its effect on skeletal health in vivo. The purpose of this study was to explore the influence of vitamin E supplementation on bone in young adult and old mice. Six and twenty-four month-old male C57BL/6NIA mice each were divided into two groups and fed a diet containing either adequate (30 mg/kg diet) or high (500 mg/kg diet) levels of vitamin E. Thirty days later, mice were killed and bones were removed for analyses including biomechanical testing using three-point bending and mRNA expressions of insulin-like growth factor-I (IGF-I), osteocalcin, and type 1alpha-collagen using Northern blot. In old but not the young adult mice, high-dose vitamin E enhanced bone quality as evident by improved material and structural bone properties in comparison with adequate. This improved quality was accompanied by increases in bone dry weight, protein, and mRNA transcripts for osteocalcin, type Ialpha-collagen, and IGF-I. These data demonstrate that high-dose vitamin E has pronounced effects on bone quality as well as matrix protein in old mice by augmenting bone matrix protein without reducing bone mineralization as evidenced by unaltered bone density.

The synthetic phytoestrogen, ipriflavone, and estrogen prevent bone loss by different mechanisms.

Abstract. Ipriflavone (IP), a synthetic isoflavone has been reported to prevent bone loss in both postmenopausal women and ovariectomized (ovx) rats. The purpose of this study was to compare and contrast some of the bone protective mechanisms of IP to those of 17β-estradiol (E2) in ovarian hormone deficiency. Forty-eight 95-day-old Sprague-Dawley rats were assigned to four groups: sham, ovx, ovx+IP, and ovx+E2. The doses of IP and E2 were 100 mg and 10 μg/kg body weight per day, respectively. Rats were fed a diet that contained 0.4% calcium, 0.3% phosphorus, and 0.195 nmol vitamin D3/g diet. After sacrifice, left femoral bone densities were measured and bone histomorphometry was performed on the proximal tibial metaphysis. Ipriflavone as well as E2 treatment completely prevented the ovx-induced femoral bone density loss. However, in contrast to E2, IP did not lower the ovx-induced rise in serum alkaline phosphatase (ALP) activity or insulin-like growth factor (IGF)-I and IGF binding protein (IGFBP)-3 concentrations. On histomorphometry analysis, the ovariectomy-induced increase (P < 0.09) in bone formation rate (BFR) was significantly (P < 0.05) suppressed by E2 treatment, whereas this higher BFR was maintained in IP-treated animals. These findings indicate that IP is effective in preventing the ovx-associated bone loss. The bone protective mechanisms of IP in ovarian hormone deficiency may be different from those of E2 and may involve increased rates of bone formation.

Soy isoflavones may protect against orchidectomy-induced bone loss in aged male rats

Evidence from several studies suggests that soy protein and/or its isoflavones may have beneficial effects on bone in postmenopausal women and animal models who have osteoporosis. The present study examined the dose-dependent effects of soy isoflavones in the context of soy protein or casein on the male skeleton. Thirteen-month-old male Fisher 344 rats were orchidectomized (ORX; 5 groups) or sham-operated (Sham; 1 group) and immediately placed on dietary treatments for 180 days. Diets were semi-purified and the protein source was either casein (Sham and ORX; controls), casein with two added doses of isoflavones (Iso1; 600 mg/kg diet and Iso2; 1200 mg/kg diet), soy protein with normal isoflavones content (Soy; 600 mg/kg diet), or soy protein with added isoflavones (Soy+; 1200 mg/kg diet). A 7% loss of whole body bone mineral density (BMD) was observed due to orchidectomy; however, the ORX induced BMD loss was significantly reduced to 4.3 and 4.7 % with the Soy and Soy+, respectively. Both doses of isoflavones in conjunction with casein also reduced the loss of whole body BMD, albeit not significantly different from ORX control animals. Trabecular bone histomorphometric analysis of the proximal tibia further supported the bone-sparing role of soy isoflavones as indicated by higher percent bone volume and trabecular number, and lower trabecular separation. We conclude that isoflavones exert modest beneficial effects on the male skeleton whether provided with casein or a soy protein.

Prune suppresses ovariectomy-induced hypercholesterolemia in rats

Elevated cholesterol among women who have experienced natural or surgical menopause has been linked to ovarian hormone deficiency. The purpose of this study was to investigate the efficacy of prune, a good source of dietary fiber and phytochemicals, on lowering cholesterol in an ovariectomized (ovx) rat model. Forty-eight 90-day-old female Sprague-Dawley rats were randomly assigned to four groups: sham-operated (sham) + control diet, ovx + control diet, ovx + low-dose (LD; 5%) prune, and ovx + high-dose (HD; 25%) prune. After 45 days of treatment, rats were euthanized and tissues were collected for analyses. Ovariectomy elevated serum total cholesterol by 22% compared with sham, and HD prune diet prevented this increase without affecting high density lipoprotein cholesterol concentrations. Animals fed the HD prune diet had 13% lower liver total lipids compared with ovx animals. The findings of this study showed that prune exhibits hypocholesterolemic properties in ovarian hormone deficiency. Dose-response studies should be conducted to establish the effectiveness of prune in prevention of hypercholesterolemia in postmenopausal women who are not on estrogen replacement therapy and seek dietary alternatives. Mechanistic studies also are needed to establish its mode of action.

The ovarian hormone deficiency-induced hypercholesterolemia is reversed by soy protein and the synthetic isoflavone, ipriflavone

The purpose of this study was to compare the effects of soy protein isolate with normal isoflavone content (soy) and with reduced isoflavone content (soy-), ipriflavone (IP), a synthetic isoflavone; and 17β-estradiol (E2) on lipid metabolism in ovariectomized (ovx) rats. Seventy-two 95-day old Sprague-Dawley rats were assigned to six groups: sham operated (sham), ovx, ovx+soy, ovx+soy-, ovx+IP, and ovx+E2. Rats in the sham, ovx, ovx+IP, and ovx+E2 groups were fed a casein-based diet, whereas the soy and soy- groups were fed diets in which casein was replaced with soy or soy-. Animals were pair-fed to the mean food intake of ovx+E2 for 35 days. At the end of the study, animals were sacrificed in a nonfasted state and blood was collected via abdominal aorta. The ovx-induced increase in serum total cholesterol was reversed by all the treatments including ipriflavone and soy. Serum triglyceride levels were not significantly affected by any of the treatments. Liver cholesterol (μmol/g) in animals receiving IP or fed soy were significantly (p<0.01) lower than the ovx, ovx+soy-, and ovx+E2 groups. Liver lipids (mg/g) were significantly (p<0.05) lower in the animals that received E2 or fed soy, but not those which were fed soy- or given IP. The ovx-induced increase in abdominal fat was completely reversed by soy and E2 treatments but not by soy- or ipriflavone treatments. Soy, soy-, and IP had no uterotrophic activity as compared to E2. Ovariectomy significantly increased body weight gains which were not suppressed by any of the treatments except E2. These data indicate that ipriflavone is effective in preventing the unfavorable changes in serum and liver cholesterol associated with ovarian hormone deficiency in this animal model. Moreover, the consumption of synthetic or natural isoflavones may offer a potential alternative therapy in the treatment of hypercholesterolemia in ovarian hormone-deficient women.

Lifestyle and Advanced Glycation End Products (AGEs) Burden: Its Relevance to Healthy Aging

Uncontrolled continued exposure to oxidative stress is a precursor to many chronic diseases including cancer, diabetes, degenerative disorders and cardiovascular diseases. Of the many known mediators of oxidative stress, reactive oxygen species (ROS) and advanced glycation end products (AGEs) are the most studied. In the present review, we have summarized current data on the origin of circulating AGEs, discussed issues associated with reliable assessment of its steady state level, and changes in its level with age and select metabolic diseases. Lastly, we have made recommendations about life style changes that may decrease AGEs burden to promote healthy aging.

Effect of Blueberry Polyphenols on 3T3-F442A Preadipocyte Differentiation

Today obesity is an epidemic, and its prevalence has increased significantly over the last few decades. To avoid excessive accumulation of fat, optimum energy intake along with regular exercise is mandatory. Polyphenols present in green tea, grape seeds, orange, and grapefruit combat adipogenesis at the molecular level and also induce lipolysis. However, very little is known regarding the role of blueberry polyphenols on adipocyte differentiation. Hence we tested the dose-dependent effects of blueberry polyphenols on mouse 3T3-F442A preadipocyte differentiation and lipolysis. 3T3-F442A preadipocytes were incubated with three doses of blueberry polyphenols (150, 200, and 250 μg/mL [BB-150, BB-200, and BB-250, respectively]), and intracellular lipid content, cell proliferation, and lipolysis were assayed. Blueberry polyphenols suppressed adipocyte differentiation determined by Oil Red-O staining and AdipoRed assay. Intracellular lipid content in control (11,385.51±1,169.6 relative fluorescence units) was significantly higher (P<.05) than with the three doses of blueberry polyphenols (8336.86±503.57, 4235.67±323.17, and 3027.97±346.61, respectively). This corresponds to a reduction of 27%, 63%, and 74%, respectively. Cell proliferation was observed to be significantly higher in the control (0.744±0.035 optical density units) than with BB-150 (0.517±0.031), BB-200 (0.491±0.023), and BB-250 (0.455±0.012). However, when tested for lipolysis, there was no significant difference observed among the groups. We conclude that blueberry polyphenols may play an effective role in inhibiting adipogenesis and cell proliferation.