1 Soyfoods are a unique dietary source of isoflavones, a phytoestrogen that may offer women heart health benefits and may help alleviate hot flashes during menopause. Soyfoods offer health benefits for all consumers, but studies show that postmenopausal women may reap particular benefits. This fact sheet discusses recent research into the benefits and safety of soy for women, from heart disease to hot flashes. Traditional soyfoods such as tofu and miso have been widely used in many East Asian countries for centuries and have been consumed by health-conscious individuals in Western countries for several decades. In recent years, because of the purported health benefits, increased numbers of Westerners have decided to incorporate soy into their diets. Soyfoods hold particular appeal for postmenopausal women because they are such uniquely rich sources of isoflavones, one type of phytoestrogen. Isoflavones exhibit estrogen-like effects under certain experimental conditions and are posited to reduce the risk of coronary heart disease, 1 osteoporosis, 2 certain forms of cancer 3 and may alleviate menopause- related hot flashes. 4 Consequently, many women view soyfoods as natural alternatives to conventional hormone therapy. Women who use alternative therapies express a desire to have control over their symptoms and the way in which their menopause is treated. 5 Not surprisingly, interest in alternative therapies increased following the publication of results of the Women’s Health Initiative (WHI) trial in 2002, which showed that the risk of long-term use of combined hormone therapy (estrogen plus progestin) outweighed the benefits. 6 In 2010, 11-year follow up data from the WHI trial found not only that combined hormone therapy increases breast cancer risk but also breast cancer mortality. 7 However, isoflavones themselves are not without controversy. Their estrogen-like effects have raised concern that these soybean constituents possess some of the same undesirable properties as hormone therapy. In particular, there is controversy over whether soyfoods are contraindicated for women who have breast cancer or who are at high risk of developing breast cancer. 8 Overview of Isoflavones Isoflavones have a limited distribution in nature. In fact, diets that do not include soyfoods are almost devoid of these compounds. 9 Not surprisingly, whereas average isoflavone intake among adults ranges from about 30-50 mg/day in Japan and Chinese cities such as Shanghai, 10 intake is less than 3 mg/day in the United States and other Western countries. 11, 12, 14-17 Using weighted, 2-day food consumption data for the U.S. population from the National Health and Nutrition Examination Survey (NHANES) 2007- 2008, the United States Department of Agriculture recently estimated that daily per capita isoflavone intake is 0.68 mg/day. 18 Isoflavones occur in soybeans as glycosides (a sugar molecule is attached to the isoflavone backbone); 19 upon ingestion, the sugar is hydrolyzed thereby allowing absorption to occur. 20 In fermented soyfoods such as miso, tempeh and natto, substantial amounts of the isoflavones occur as aglycones due to bacterial hydrolysis. The three isoflavones genistein, daidzein and glycitein and their respective glycosides account for approximately 50 percent, 40 percent and 10 percent, respectively, of the total isoflavone content of soybeans. 19 Each gram of soy protein in soybeans and traditional soyfoods is associated with approximately 3.5 mg of isoflavones. 10 In this document, isoflavone amounts are expressed in aglycone equivalent weights. Consequently, one serving of a traditional soyfood, such as 3-4 oz of tofu or 1 cup of soymilk, typically provides about 25 mg of isoflavones. Soy protein is present in a wide range of commonly consumed foods in the U.S. However, isoflavone exposure from these foods is almost negligible for two reasons. First, the amount of soy protein in these foods is quite small because it is added for functional (not nutritional) purposes such as bleaching, moisture retention, oxidation inhibition and improved texture. And second, the isoflavone concentration of the soy protein used in this way is generally quite low in comparison to traditional soyfoods. The isoflavone-to-protein ratio noted above for traditional soyfoods does not apply to many processed forms of soy. Soy WOMEN Soy connection fact Sheet by the united Soybean board 2 In most clinical trials, hot flash relief is achieved by ingesting approximately 50 mg total isoflavones daily. Soyfoods are unique because they are rich dietary sources of isoflavones, which are endocrine active substances but different from the hormone estrogen. Isoflavones are diphenolic compounds with a chemical structure similar to the hormone estrogen; they bind to both estrogen receptors alpha and beta – ERα and ERβ. 21, 22 For this reason, they are commonly referred to as phytoestrogens. Their relative binding affinity is lower than that of estrogen (17β-estradiol), but circulating levels of isoflavones in people consuming soyfoods are approximately three orders of magnitude higher than levels of estrogen. 23 While estrogen binds to and transactivates both ERα and ERβ equally, isoflavones preferentially bind to and transactivate ERβ. 24-27 This difference in binding and transactivation between isoflavones and estrogen is important because the two estrogen receptors have different tissue distributions and, when activated, can have different and sometimes even opposite physiological effects. This appears to be the case in the breast, where ERβ transactivation is thought to inhibit the proliferative effects of ERα transactivation. 28, 29 The preference of isoflavones for ERβ is one reason they exert tissue- selective effects, and for this reason, isoflavones are classified as selective estrogen receptor modulators (SERMs). 30-32 In tissues that possess estrogen receptors, SERMs exert estrogen-like effects in some cases but no effects or antiestrogenic effects in others. The pharmaceutical industry has for many years been actively developing SERMs. 33 Widely used SERMs include tamoxifen, used in breast cancer treatment, and raloxifene, which is used for treatment of osteoporosis. 34 In addition to being classified as phytoestrogens and SERMs, the European Food Safety Authority has recently proposed a new classification for compounds such as isoflavones, which is “endocrine active substances.” 35 From the above discussion, it is clear that isoflavones should not be equated with the hormone estrogen. The clinical literature is replete with examples of differences between these two molecules. 32, 36-56 Furthermore, isoflavones may exert potentially-relevant hormone-independent physiological effects. Therefore, the classification related to their hormonal activity may be an incomplete characterization. 57 Finally, not only should isoflavones not be equated with estrogen but soyfoods should not be equated with isoflavones. This is because the soybean, like all foods, is a collection of hundreds of biologically active molecules. 58 Soy, Isoflavones and Hot Flashes Hot flashes are the most common reason given by women seeking treatment for menopausal symptoms. For the majority of women who experience them, hot flashes begin prior to menopause. Ten to 15 percent of these women experience hot flashes that are severe and frequent. 59 Although hot flashes usually subside after six months to two years, 59, 60 many women report having them for up to 20 years after menopause. 61 The etiology of hot flashes is not fully understood but the drop in circulating estrogen levels that occurs during menopause is recognized as one factor. The low incidence of hot flashes in Japan gave rise to initial speculation that isoflavones could be useful in their prevention. 62 Even Chinese-American and Japanese-American women are about one-third less likely to report experiencing hot flashes than Caucasian women. 63 Interestingly, among Asian women, chilliness and shoulder aches are much more commonly reported menopausal symptoms than hot flashes. Recent evidence suggests, however, that Japanese women are reluctant to report having hot flashes. 64 To this point, one study found that hot flash frequency was lower among Japanese compared to Caucasian women when based on a subjective determination (personal diary), but not when determined objectively by measuring sternal and nuchal skin conductance. 65 Sources of Soy Protein Soyfood Serving size Grams of soy protein Fortified soymilk 1 cup 6-7 Soy cereal 1 ¼ cup 7 Soy yogurt, vanilla 1 cup 6 Soy breakfast patty 2 patties 11 Soy bar 1 bar 14 Soy chips 1 bag 7 Soynut butter 2 Tbsp 7 Soynuts, roasted, unsalted ¼ cup 11 Tofu ½ cup 10 Edamame ½ cup 11 Soy burger 1 patty 13-14 Soy pasta ½ cup (cooked) 13 Soy pudding ½ cup 6 3 isoflavones is consistent with the degree of benefit deemed satisfactory by women seeking non-hormonal treatments for hot flashes. 76 The amount of isoflavones providing symptom relief is found in approximately two servings of traditional soyfoods. Osteoporosis In response to declining estrogen levels, women can lose substantial amounts of bone mass in the decade following menopause, which markedly increases their fracture risk. 77 Estrogen therapy reduces postmenopausal bone loss and hip fracture risk by approximately one-third. 6 Recent data shows that the protective effects against hip fracture are lost within two years of cessation of estrogen therapy. 78 Initial speculation that soyfoods might promote bone health in postmenopausal women was based on the estrogen-like effects of isoflavones and early research showing that the synthetic isoflavone, ipriflavone, exerted skeletal benefits. 79 Since 1995, more than 50 clinical trials have examined the impact of isoflavone-rich soyfoods or isoflavone supplements on the alleviation of menopause-related hot flashes. In recent years, investigators have gravitated toward the use of supplements rather than soyfoods to enhance compliance and reduce the complexity of study design. The results of these trials have produced inconsistent results. Although some recent reviews and analyses of the literature have concluded that isoflavone-rich products alleviate hot flashes, 4, 66 most have found that the data does not allow for definitive conclusions to be made even though more trials than not showed benefit. 67, 68 Some inconsistency in the literature is expected given the small sample size of many trials and the variable placebo response. However, several more specific explanations for the seemingly inconsistent data have been proposed, including intraindividual differences in isoflavone metabolism, 69 differences in baseline hot flash frequency (i.e., isoflavones are more effective in women with more frequent hot flashes) 66 and differences in the isoflavone content or profile of the intervention products (i.e., products containing higher amounts of genistein are deemed to be most effective). 70 In response to the ingestion of the same amount of isoflavones, serum levels of isoflavones and their metabolites differ by a factor of several hundred among individuals. 20, 71 Therefore, it is reasonable to speculate that differences in metabolism can affect the response to soyfoods, at least for health outcomes thought to be affected by isoflavones. However, this explanation appears to be more applicable to differences between individual women’s experiences and less likely to explain why large-scale studies would report variable outcomes. In contrast, differences in the isoflavone content of the intervention products appear more applicable to differences in results among studies. Some of the inconsistency may also be because the two main soy-derived isoflavone supplements that are available commercially and that have been used in the clinical trials have markedly different isoflavone profiles. 72 One is high in genistein and daidzein but low in glycitein, which is similar to the isoflavone profile of soyfoods, whereas the other is very low in genistein and high in daidzein and glycitein. Several lines of evidence, including relative estrogen receptor binding and transactivation, indicate that genistein is more potent than daidzein or glycitein and there is evidence that genistein is more potent than the other isoflavones for alleviating hot flashes. 73, 74 The most comprehensive statistical analysis of the literature, which was only recently published, clearly supports the efficacy of isoflavones for alleviating hot flashes. 75 This systematic review and meta-analysis included 19 and 17 studies, respectively, and included only studies involving isoflavone supplements derived from soy. The meta-analysis of the data on hot flash frequency, which included 13 studies involving 1,196 women, found isoflavones were consistently efficacious, reducing the number of hot flashes per day about 21 percent more than the reduction in the placebo group. Similarly, in the nine trials involving 988 women that evaluated hot flash severity, isoflavones reduced symptoms by about 26 percent more than the reduction in the placebo group. For both measures, the effect of isoflavones was highly statistically significant. When considering the combined effect of the placebo and isoflavones, the overall reduction in frequency and severity was approximately 50 percent. Furthermore, subanalysis indicated that isoflavone supplements providing at least 18 mg genistein were more than twice as efficacious as supplements lower in genistein. As noted previously, genistein is the predominant isoflavone in soybeans. Collectively, this data makes a convincing case that isoflavones can be of help to women who experience hot flashes. The level of relief provided by The relatively low hip-fracture rates in Asian countries have also been cited as evidence for the skeletal benefits of isoflavones, but other factors may help explain these rates. 80 For example, Asians have a shorter hip axis length, which reduces risk for fracture. 81, 82 Also, Japanese women are less likely than Western women to fall, the precipitating event for hip fracture. 83, 84 However, spinal bone mineral density (BMD) and spinal fracture rates are similar between Asians and Caucasians. 85-92 Nevertheless, the available evidence shows that, among Chinese women, high soy consumers are less likely to report having a fracture. Fortified soymilk is a good source of isoflavones and also contains calcium, vitamin D and protein, which offer additional bone health benefits. 4 Two prospective epidemiologic studies have evaluated the relationship between soy intake and fracture risk. In both, risk was reduced by approximately one-third when women in the highest soy intake quintile or quartile were compared to women in the lowest. This degree of protection is similar to that noted for estrogen therapy. 6 In one of the prospective studies, approximately 1,800 fractures of all types occurred in the 24,000 postmenopausal Shanghai women who were followed for 4.5 years. 93 In the other, there were almost 700 hip fractures (the only site studied) among the 35,000 postmenopausal Singaporean women during the 7-year follow up period. 94 In a third prospective epidemiologic study involving Seventh-day Adventists, a religious denomination that includes a high proportion of vegetarians, soymilk intake was significantly inversely related to osteoporosis. 95 In this study, which involved 337 postmenopausal women, participants had their bone health assessed using broadband ultrasound attenuation of the calcaneus two years after completing a lifestyle and dietary questionnaire at enrollment. Compared with women who did not drink soymilk, women drinking soymilk once a day or more had 56 percent lower odds of osteoporosis (defined as defined as a T-score <-1.8). However, the protective effect of soymilk was likely due to its calcium rather than isoflavone content since dairy product intake was similarly protective. Although the results of these three studies are intriguing, definitive conclusions about the skeletal effects of soyfoods can only be based on the results from appropriately designed clinical studies. Since the first clinical study to examine the effects of an isoflavone-rich product on bone mineral density (BMD) in postmenopausal women was published in 1998, 96 more than 25 trials have provided results (for reviews, see references) although many involved small numbers of subjects and were conducted for relatively short durations. 97, 9 8 Ideally, studies of bone health should be at least 2-3 years in duration. The results from the clinical research thus far has been mixed, as recently published meta-analyses of the data concluded that isoflavones reduce bone breakdown 99 and increase both bone formation 99 and spinal BMD 2, 100 in postmenopausal women. However, a more rigorously-conducted meta-analysis failed to provide support for the skeletal benefits of isoflavones. 101 Among the many clinical trials, one of the longest (two years) and largest (304 subjects) published to date found that postmenopausal Italian women with osteopenia who were assigned to the placebo group lost approximately 6 percent of their BMD at the spine and hip, whereas those women in the genistein group (54 mg/day genistein aglycone provided as a supplement) gained approximately this much bone at both skeletal sites. 54 Although intended to last only two years, approximately half of the subjects agreed to continue for a third year; the differences between groups in the third year were even more striking. 102 However, these results stand in stark contrast to several recently conducted trials. For example, a 1-year study involving women from three European countries failed to show that isoflavone supplements (110 mg/ day) inhibited bone loss in early postmenopausal women. 103 In agreement, another 1-year trial failed to show that either isoflavone supplements or isoflavone-rich soy protein affected bone loss in U.S. postmenopausal women. 104 Similarly, a recently published 2-year study found that soy protein, regardless of isoflavone content, failed to prevent bone loss in postmenopausal women, although this study had a large dropout rate and many women were non-compliant with the intervention. 105 According to the American Cancer Society, breast cancer patients can consume up to 3 servings of soyfoods daily. Lastly, the most important results were from three very large studies, two of which were two years 106, 107 in duration whereas the third was three years in duration. 108 Two of these were conducted in the U.S. 106, 107 and one in Taiwan. 108 Isoflavone intake from supplements was 80 and 120 mg/day in one study, 109 200 mg/day in another 107 and 300 mg/day in the third. 108 The results from these trials provide no support for the skeletal benefits of isoflavones and they agree with those from a trial that utilized a novel methodology to examine the effects of estrogen and a variety of phytoestrogen supplements on bone reabsorption. Only at very high doses – doses exceeding typical isoflavone exposure from soyfoods – was there any evidence of antiresorptive effects. 73 It is unclear why the previously mentioned Italian study 102 found such protective effects of genistein, in contrast to other studies using mixed isoflavones that would have provided similar amounts of genistein. Also unclear is why the two Chinese prospective epidemiologic studies found soy intake was so protective against fracture. It is possible that those subjects who consumed soyfoods also led an overall healthier lifestyle (the “healthy user effect”). Yet, since soyfoods are traditional foods in Asian countries, this is less likely to be the explanation than it would be in non- 5 At study termination, progression among the women consuming soy was 16 percent lower than in the milk group. While the difference was not statistically significant, the results are intriguing. If a 16 percent decrease in the progression of CIMT translates into a 16 percent decrease in the risk of future coronary events, the public health implications would be dramatic. Furthermore, the difference between groups increased steadily over the 3-year study period. This suggests that after a longer period of soy exposure, progression would have been reduced to an even greater extent, and with it, risk of coronary events. Additionally, subanalysis of the results revealed that among women who were fewer than 5 years, 5-10 years, and more than 10 years post- menopause, CIMT progression was reduced by 68 (p=0.05), 17 (p=0.51) and 9 percent (p=0.77), respectively. It is notable that progression was reduced so significantly in early postmenopausal women for two reasons. First, it adds substantially to the biological plausibility of the findings, and second, it provides clear insight into the soy component responsible for the beneficial effects. The pronounced effect in early menopausal women suggests isoflavones were primarily responsible for the reduced CIMT progression. Over the past 10 years, a hypothesis has emerged, referred to as the “estrogen timing hypothesis.” This maintains that exposure to estrogen-like compounds leads to dramatic coronary and cognitive benefits when begun soon after menopause, but has less effect in later years. 125 Asian countries where soyfoods are generally perceived as health foods. Another explanation is that in the epidemiologic studies, isoflavone intake occurred via the consumption of traditional soyfoods, whereas the clinical studies have generally used soy extracts. However, there is no evidence that this difference matters with respect to skeletal effects. It may also be that the effects noted in the epidemiologic studies result from lifelong intake as opposed to the relatively short-term intervention periods begun in adulthood in the clinical studies. At the same time, there is no direct evidence supporting this suggestion. At this point, the evidence that isoflavones provide skeletal benefits is unimpressive. Soyfoods have other benefits in this regard, however, since they provide high quality protein, 110 which may promote bone health. 111, 112 In addition, some are good sources of calcium as well as vitamin D. 113 Importantly, the absorption of calcium from calcium-set tofu 114 and calcium-fortified soymilk 113, 115 is comparable to the absorption of this mineral from cow’s milk. Heart Health Soyfoods potentially offer protection against heart disease through several different mechanisms. Soyfoods are low in saturated and high in polyunsaturated fat. 116 In addition, soy protein directly lowers blood cholesterol levels, an attribute that was formally recognized by the U.S. Food and Drug Administration in 1999. 117 Estimates are that, via the fatty acid profile and soy protein content, when soyfoods replace conventional sources of protein in Western diets, blood low-density-lipoprotein (LDL) cholesterol levels will be lowered by about 8 percent. In theory, over a period of years, this may reduce risk of coronary heart disease (CHD) by 8-16 percent. 118 There is also evidence that, independent of effects on blood cholesterol, soyfoods may reduce CHD risk. For example, four recently published meta-analyses found that soy lowered blood pressure. 119-122 Furthermore, isoflavones improve impaired endothelial function in postmenopausal women. 123 Lastly, the most important study came from the Women’s Isoflavone Soy Health (WISH). This 3-year study involved 350 healthy postmenopausal women ages 45-92, and found that isoflavone-rich soy protein inhibited the progression of subclinical atherosclerosis. 124 Subclinical atherosclerosis can be assessed using ultrasound to measure the thickness of the carotid arteries—which are located on both sides of the neck beneath the jawline and provide the main blood supply to the brain. The thickness of the carotid artery is referred to as carotid intima- media thickness or CIMT. Typically, CIMT increases or progresses over time; the extent of progression reflects risk of future coronary events. Participants in the WISH study were randomly assigned to groups consuming either 25 g of isolated soy protein per day or 25g of milk protein. The soy protein provided 99 mg of isoflavones (expressed in aglycone equivalent weight). Soyfoods may offer protection against heart disease, as they are low in saturated fat and high in polyunsaturated fats. 6 Breast Cancer There has been rigorous investigation of the role of soyfoods in reducing breast cancer risk. A recent meta-analysis found that, in Asian epidemiologic studies, higher soy intake was associated with a 29 percent decreased risk of breast cancer. 3 However, there is solid evidence indicating that to derive this benefit, soy consumption must occur during childhood or adolescence. 126-128 In animal studies, when very young rodents are exposed to isoflavones, breast or mammary cells undergo a change that makes them permanently less likely to be transformed into cancer cells later in life. 126, 129-131 This proposed mechanism may be similar to that proposed for the protective effect of early pregnancy against breast cancer. 132 Despite the proposed benefits, the relationship between soyfoods and breast cancer is controversial due to concern, based almost exclusively on in vitro and rodent data, that isoflavones may be contraindicated for women with breast cancer or who are at high risk of developing breast cancer. 133 The position of the American Cancer Society is that women with breast cancer can safely consume up to three servings of traditional soyfoods daily. 134 However, their review of this issue was rather brief and was conducted prior to the publication of important clinical and epidemiologic data. A review of the breast cancer controversy is presented below. At high concentrations, the isoflavone genistein inhibits the growth of estrogen-sensitive breast cancer cells in vitro, whereas at lower, more physiologic concentrations, growth is stimulated. 135 More importantly, isoflavone-containing products have been found to stimulate the growth of mammary tumors in ovariectomized athymic mice implanted with estrogen-sensitive breast cancer cells. 136 Stimulation appears to result primarily from exposure to the isoflavone genistein. 137 In this model, genistein was also found to inhibit the efficacy of tamoxifen and the aromatase inhibitor, letrozole. 138 Interestingly, more highly processed soy products stimulate tumor growth to a greater extent than less processed ones, despite containing similar amounts of genistein. 139 In fact, soy flour, the least processed product to be evaluated, does not result in tumor stimulation. However, the relevance of this processing effect is in question because it has now been established that, in athymic mice, processing affects genistein pharmacokinetics in a way that leads to greater tumor stimulation, which is not the case in humans. 140, 141 Also, Japanese researchers, using the previously described mouse model, found that genistein did not stimulate tumors. 142 Prior to implantation, the cancer cells were cultured in estrogen-free media, whereas in the model which found that genistein stimulated tumors, cells were cultured in media containing a high concentration of estrogen. The Japanese researchers maintain that the latter is unphysiologic and makes the cells hypersensitive to estrogenic molecules. Clearly, there are limitations to animal research and resolving the soy and breast cancer controversy will require human data. The pertinent human data suggest that isoflavones do not exert stimulatory effects on breast tissue. Isoflavones do not increase breast tissue density or breast cell proliferation in vivo, both of which are markers of breast cancer risk. 143 In contrast, combined menopausal hormone therapy, which increases breast cancer risk, increases breast cell proliferation four-fold within just 12 weeks. 144, 145 Thus, the clinical data are supportive of safety, but the lack of effects in these studies also argues that adult soy intake does not reduce breast cancer risk at this point in life. The lack of harmful effects noted in the clinical studies are consistent with the results from four prospective epidemiologic investigations. They examined the impact of post-diagnosis soyfood intake on the prognosis in women who have had breast cancer. The first study was designed to specifically examine the soy and breast cancer controversy. Data from the Shanghai Breast Cancer Survival Study (SBCSS), 146 a population-based cohort study of breast cancer survivors, were analyzed to investigate the effect of soy intake after diagnosis on breast cancer prognosis. 147 During the median follow-up period of approximately 3.9 years, the hazard ratio associated with the highest quartile of soy protein intake was 0.71 for total mortality and 0.68 for recurrence compared with the lowest quartile of intake. In fact, in this study, high soy intake was as protective as tamoxifen use. In the second study, which was conducted in the U.S. and involved nearly 2,000 breast cancer patients, over the 6-year follow-up period, results suggested that isoflavone intake may have improved prognosis overall, and, in particular, among those women taking tamoxifen. 148 However, among patients who had not previously used tamoxifen, there was an increased risk associated with higher genistein intake but relatively few women fell into this category. This raises the possibility that these findings may have occurred by chance. In a second Chinese study, Human data suggests that isoflavones do not exert stimulatory effects on breast tissue, such as tissue density or cell proliferation in vivo, which are both markers of breast cancer risk. Clinical evidence indicates that neither soyfoods nor isoflavones adversely affect breast tissue. 7 which was conducted in Harbin among postmenopausal women with estrogen receptor positive and progesterone receptor positive tumors, soy consumption was associated with an approximate 30 percent decrease in recurrence although overall mortality was not affected. 149 Interestingly, although there was no interaction between tamoxifen and soy intake, which is consistent with the results of the SBCSS, soy intake enhanced the efficacy of anastrozole, an aromatase inhibitor. These findings are important in and of themselves, and also because they contradict the findings in animals. Finally, the most recently published U.S. study involved 2,736 breast cancer survivors diagnosed between 1991 and 2000 with early stage breast cancer who were participants in the Women’s Healthy Eating and Living study. 116 During the median 7.3-year follow-up period, there were 448 new breast cancer events and 271 deaths. The results showed that as isoflavone intake increased, risk of death decreased. Women in the highest isoflavone intake category (cutoff, >16.3 mg/day; median 26.7 mg/day) had a 54 percent reduction in risk of death (p for trend=0.02). The benefits of isoflavone intake were most evident in women being treated with tamoxifen. A recent commentary in the journal Women’s Health concluded that there is no longer any justification for advising women with breast cancer to avoid soyfoods. 150 However, the data also does not justify a recommendation that women should consume soyfoods specifically to improve prognosis. Rather, the recommendation should be that women with breast cancer who currently consume soyfoods or wish to consume them can safely do so. Nevertheless, breast cancer patients should discuss any dietary changes with their primary healthcare provider. References 1. Messina M, Lane B. Soy protein, soybean isoflavones, and coronary heart disease risk: Where do we stand? Future Lipidology. 2007; 2: 5 5-74. 2. Ma DF, Qin LQ, Wang PY, Katoh R. Soy isoflavone intake increases bone mineral density in the spine of menopausal women: Meta-analysis of randomized controlled trials. Clin Nutr. 2008; 27: 57-64. 3. Wu AH, Yu MC, Tseng CC, Pike MC. Epidemiology of soy exposures and breast cancer risk. Br J Cancer. 2008; 98: 9-14. 4. Howes LG, Howes JB, Knight DC. Isoflavone therapy for menopausal flushes: a systematic review and meta-analysis. Maturitas. 2006; 55: 203-11. 5. Gollschewski S, Kitto S, Anderson D, Lyons-Wall P. Women’s perceptions and beliefs about the use of complementary and alternative medicines during menopause. Complement Ther Med. 2008; 16: 163-8. 6. Writing Group for the Women’s Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA. 2002; 288: 321-33. 7. Chlebowski RT, Anderson GL, Gass M, Lane DS, Aragaki AK, Kuller LH, Manson JE, Stefanick ML, Ockene J, et al. Estrogen plus progestin and breast cancer incidence and mortality in postmenopausal women. JAMA. 2010; 304: 1684-92. 8. Helferich WG, Andrade JE, Hoagland MS. Phytoestrogens and breast cancer: a complex story. Inflammopharmacology. 2008; 16: 219-26. 9. Franke AA, Custer LJ, Wang W, Shi CY. HPLC analysis of isoflavonoids and other phenolic agents from foods and from human fluids. Proc Soc Exp Biol Med. 1998; 217: 263-73. 10. Messina M, Nagata C, Wu AH. Estimated Asian adult soy protein and isoflavone intakes. Nutr Cancer. 2006; 55: 1-12. 11. Horn-Ross PL, John EM, Canchola AJ, Stewart SL, Lee MM. Phytoestrogen intake and endometrial cancer risk. J Natl Cancer Inst. 2003; 95: 1158-64. 12. Goodman-Gruen D, Kritz-Silverstein D. Usual dietary isoflavone intake is associated with cardiovascular disease risk factors in postmenopausal women. J Nutr. 2001; 131: 1202-6. 13. 2004Q-0151: Qualified Health Claim (QHC): Soy Protein and Cancer (http://www.fda.gov/ohrms/dockets/ dockets/04q0151/04q0151.htm). 14. de Kleijn MJ, van der Schouw YT, Wilson PW, Adlercreutz H, Mazur W, Grobbee DE, Jacques PF. Intake of dietary phytoestrogens is low in postmenopausal women in the United States: the Framingham study (1-4). J Nutr. 2001; 131: 1826-32. 15. van Erp-Baart MA, Brants HA, Kiely M, Mulligan A, Turrini A, Sermoneta C, Kilkkinen A, Valsta LM. Isoflavone intake in four different European countries: the VENUS approach. Br J Nutr. 2003; 89 Suppl 1: S25-30. 16. van der Schouw YT, Kreijkamp-Kaspers S, Peeters PH, Keinan-Boker L, Rimm EB, Grobbee DE. Prospective study on usual dietary phytoestrogen intake and cardiovascular disease risk in Western women. Circulation. 2005; 111: 465-71. 17. Boker LK, Van der Schouw YT, De Kleijn MJ, Jacques PF, Grobbee DE, Peeters PH. Intake of dietary phytoestrogens by Dutch women. J Nutr. 2002; 132: 1319-28. 18. Haytowitz DB, Bhagwat S. Assessment of sources and dietary intake of isoflavones in the U.S. diet (poster presentation). 9th international symposium on the role of soy in health promotion and chronic disease prevention and treatment (Washington, DC, October 16-19, 2010). 19. Murphy PA, Barua K, Hauck CC. Solvent extraction selection in the determination of isoflavones in soy foods. J Chromatogr B Analyt Technol Biomed Life Sci. 2002; 777: 129-38. 20. Rowland I, Faughnan M, Hoey L, Wahala K, Williamson G, Cassidy A. Bioavailability of phyto-oestrogens. 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Margeat E, Bourdoncle A, Margueron R, Poujol N, Cavailles V, Royer C. Ligands Differentially Modulate the Protein Interactions of the Human Estrogen Receptors alpha and beta. J Mol Biol. 2003; 326: 77-92. 26. Kostelac D, Rechkemmer G, Briviba K. Phytoestrogens modulate binding response of estrogen receptors alpha and beta to the estrogen response element. J Agric Food Chem. 2003; 51: 7632-5. Soyfoods provide high quality protein and are good sources of well-absorbed protein. Summary and Conclusions Soyfoods are unique because they are rich dietary sources of isoflavones, which are endocrine active substances but different from the hormone estrogen. Epidemiologic and clinical data suggest that soyfoods can make important contributions to the health of women, particularly postmenopausal women. Soyfoods potentially reduce coronary heart disease through multiple mechanisms and may be especially beneficial when consumed by young postmenopausal women. 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The 69 farmer-directors of USB oversee the investments of the soy checkoff to maximize profit opportunities for all U.S. soybean farmers. These volunteers invest and leverage checkoff funds to increase the value of U.S. soy meal and oil, to ensure U.S. soybean farmers and their customers have the freedom and infrastructure to operate, and to meet the needs of U.S. soy’s customers. As stipulated in the federal Soybean Promotion, Research and Consumer Information Act, the USDA Agricultural Marketing Service has oversight responsibilities for USB and the soy checkoff. For more information, please visit SoyConnection.com. . above for traditional soyfoods does not apply to many processed forms of soy. Soy WOMEN Soy connection fact Sheet by the united Soybean board 2 In most clinical. percent, respectively, of the total isoflavone content of soybeans. 19 Each gram of soy protein in soybeans and traditional soyfoods is associated with