Scientific evidence of soy protein and soy isoflavones in preventing and treating chronic diseases

Not All Soy Products Are Created Equal: Caution Needed in Interpretation of Research Results

J.Nutr.134: 1229S-1233S, 2004

Interest in the health benefits of soy foods has been intense among the research community, health professionals, and the public. Levels of isoflavones are frequently assumed to be constant within categories of soy foods, and intakes are estimated rather than being directly analyzed. With the hundreds of publications yearly on soy and isoflavones, it is especially important to consider the literature in its entirely when making pronouncements about health benefits. Chemical composition of soy concentrates or isolates is affected by processing techniques, including both solubilization method and temperature.

The soybean contains 6 forms of isoflavones in aglycone forms namely daidzin, daidzein, genistin, genistein, glycitin and glycitein. Simply indicating the total isoflavone content and the form of the isoflavones in a product is not sufficient. Ideally, all values should be expressed as the aglycone equivalent. The microflora in the intestinal tract in humans produce equol, the biologically active isoflavone from daidzein in the gastrointestinal tract and outcomes of studies with rats and mice may not predict the effect of soy isoflavone consumption by humans.

Cell culture studies often use isoflavone concentrations of 10 – 1000 times higher than physiological levels and provide isoflavones without other soy components. In vitro studies may either underestimate or overestimate the in vivo potency of isoflavones, particularly for studying structure-activity relationships and mechanisms whereby soy components may affect cellular or molecular events. An underestimation may occur because in vitro systems may lack cellular factors that potentiate the effects of isoflavones in vivo or because isoflavone metabolites are produced in vivo that are more potent than the parent compound.

To reduce the confusion regarding soy and health research, the media and public health officials should look at the totality of the evidence when commenting on the potential significance of new findings and demand that researchers be clear on what soy product or extract was used and how any findings compare with the existing literature.

New Soy-Breast Cancer Study Finds Small but Significant Protective Effect

American Institute for Cancer Research, Press Release: 4 April 2006. http://www.aicr.org

The new study, “Meta-Analysis of Soy Intake and Breast Cancer Risk,” appearing in the April 5 issue of the Journal of the National Cancer Institute (JNCI) analyzes data from 18 previously published studies and concludes that among healthy women, soy consumption was associated with a small but statistically significant (14 percent) reduction in breast cancer risk.

The JNCI study supports the notion that soy has a place as one component of a cancer-protective diet high in a variety of plant foods and low in meat and dairy products. It’s no miracle food, but it offers a healthy and versatile alternative to meat that can add variety to meals. No evidence has emerged that soy stimulate tumor growth in humans although laboratory studies that have investigated the relationship between soy and breast cancer at the cellular level have uncovered some evidence that individual soy components may have the potential to stimulate tumor growth in animal models under a specific set of conditions.

The use of soy supplements that contain individual soy components (soy protein, isoflavones, etc.) was not directly addressed by the JNCI Meta-Analysis. The author of the study were careful to mention that most of the data they investigated were related to the consumption of the whole soy foods.

The authors noted that the observed reduction in breast cancer risk associated with soy foods was roughly the same (approximately 14 percent) in both Asian and Western populations. The authors suggested that this might have something to do with the fact that the two cultures tend to consume soy at different times of life. “When it comes to soy and breast cancer, the most exciting hypothesis continues to be that intake during adolescence is the key to protection, “ soy foods expert Mark Messina , Ph.D. said.

Studies found that soy could become "pro-estrogen" in women with low levels of natural estrogen. In other words, concentrated soy supplements may add estrogen to the body and hence may increase breast cancer risk in post-menopausal women. Therefore, post-menopausal women should avoid taking concentrated soy supplements until more is known. Eating soy products, however, is not harmful.

Gloria Tsang, RD. www.healthcastle.com

---

Soy Isoflavones – Benefits and Risks from Nature’s Selective Estrogen Receptor Modulators (SERMs)

Kenneth D.R. Setchell, PhD Journal of the American College of Nutrition, Vol. 20, No. 5, 354 -362S (2001)

Key teaching points:

1. Soy is the richest dietary source of bioactive phytoestrogen called isoflavones and the their bioavailability is highly dependent on intestinal bacterial metabolism
2. The pharmacokinetic behavior of isoflavones indicates that the maximal health benefits are most likely to be derived by consuming small amount of isoflavone-rich soy foods throughout the day
3. Maximal health benefits from phytoestrogen-rich foods are likely to occur from regular and lifelong consumption
4. Isoflavones have characteristics that are consistent with selective estrogen receptor modulators and not estrogen. As such, when consumed at usual dietary intakes consistent with intakes by Asians, isoflavones are unlikely to have the negative effects associated with estrogens

Perhaps the greater misnomer has been the liberal classification of soy isoflavones as ‘estrogen’. Concerns have been voiced that soy isoflavones are potentially harmful because they are ‘estrogens,’ albeit natural.

Soy isoflavones are naturally occuring estrogens have the ability to bind to estrogen receptors, as do many substances including anti-estrogens like tamoxifen used successfully to treat breast cancer due to the presence of the phenolic rings, and particularly the 4’-hydroxyl. Soy isoflavones especially the isoflavone genistein shows a higher relative affinity for binding to the ER-beta receptor, about six-to eightfold, and appear to model on selective estrogen receptor modulators (SERMs) in their conformational binding to the receptor comparable to SERM raloxifene and not like estradiol as demonstrated in elegant X-Ray Crystallographic studies. So, rather than classifying soy isoflavones as ‘estrogen’, they should more correctly be judged to act hormonally as natural SERMs and thus suggests that soy isoflavones are likely to have the beneficial effect of estrogen without the negatives, especially in tissues such as the endometrium and breast.

Perhaps the most legitimate concern is the question of whether a woman with breast cancer should be advised to avoid soy foods and phytoestrogen supplements. Recommendations to avoid soy foods now being given by many health professionals to these patients are not based on any clinical evidence to support this advice. As discussed above, the fact that an isoflavone like genistein acts more like a SERM than an estrogen should be the basis for believing that soy foods are more likely to be beneficial for breast cancer treatment and prevention. The MORE trial of raloxifine supports this view.

Hormonal Effects of Soy Isoflavones: Studies in Premenopausal and Postmenopausal Women

Mindy S. Kurzer - Department of Food Science and Nutrition, University of Minnesota, St. Paul, MN

Third International Symposium on the Role of Soy in Preventing and Treating Chronic Disease, Washington, D.C., October 31–November 3, 1999.

It has long been recognized that phytoestrogens exert hormonal effects in cell culture systems and animals, but effects in humans have not been studied until quite recently. The primary hypothesis of most researchers has been that phytoestrogens lower estrogen levels and action in the high estrogen milieu of premenopausal women and act as estrogen agonists in the low estrogen milieu of postmenopausal women. It has been proposed further that antiestrogenic effects of soy isoflavone consumption may lower breast cancer risk in premenopausal women, whereas estrogenic effects may benefit the cardiovascular system, bone and vasomotor systems in peri and postmenopausal women. Thus, hormonal effects might explain epidemiologic observations of lowered risk of chronic diseases and menopausal symptoms in populations that consume soy.

The major effects in premenopausal women consuming isoflavone-rich soy protein include decreased midcycle luteinizing hormone and follicle-stimulating hormone concentrations; increased menstrual cycle length ; and decreased urinary estrogens, with a preferential decrease in proposed genotoxic estrogen metabolites. Increased menstrual cycle length and decreased urinary estrogen excretion may suggest reduced exposure to estrogen, and both have been associated with lowered risk of breast cancer. On the other hand, soy consumption has been observed to both increase and decrease plasma estrogen concentrations; one study reported increased nipple aspirate volume , suggesting estrogenic effects on the breast. Other observations include no effects on endometrial biopsy results or plasma sex hormone-binding globulin concentrations. These effects appear to be due at least in part to the soy isoflavones.

Few hormonal effects have been reported in postmenopausal women consuming soy isoflavones. The major effects reported in postmenopausal women consuming 34–165 mg/d of isoflavones in isoflavone-rich soy protein, soy flour or soy foods include increased sex hormone–binding globulin, a modest decrease in the frequency and severity of hot flushes and vaginal dryness, and a slight increase in vaginal cell maturation. One study showed decreased estrogens and no effects on endometrial biopsy results. These results suggest that soy consumption exerts modest estrogenic effects, likely as a result of the presence of soy isoflavones. Thus, soy consumption appears to exert modest hormonal effects in both pre- and postmenopausal women. The effects are generally in the direction of providing health benefits, although they are quite small and of uncertain clinical significance. Further research must be performed to clarify the magnitude and significance of the hormonal effects of soy consumption, and, if effects are seen, to establish whether the responsible components are the isoflavones or some other soy constituent.