Soy Isoflavones Pennington Biomedical Research Center Division of

Soy Isoflavones Pennington Biomedical Research Center Division of Education Heli J. Roy Ph. D Shanna Lundy, BS Phillip Brantley, Ph. D, Director PBRC 2005 1

General info… • Soy is a low cost source of protein that has been consumed in Asian nations for many centuries • Regular intake of this food is thought to be partially responsible for the lower rates of heart disease, stroke, and cancer observed in Eastern populations. PBRC 2005 2 of 28

Information. . • Isoflavones are members of the large flavonoid family of plant compounds which are, in turn, members of the larger group of plant constituents known as polyphenols • The principal isoflavones in soy are genistein, daidzein, and their metabolites Genistein Daidzein PBRC 2005 3 of 28

Good sources of Soy… • Edamame or Soy beans: Soy beans are the least processed form of soy protein. They are available in most grocery stores and can be purchased in fresh, frozen, or roasted forms • Tofu: Tofu, or bean curd, is made my curdling soymilk with a coagulant. Tofu can be used in a variety of recipes to partially replace either meat or dairy products. Because calcium sulfate is often used as the curdling agent, tofu is also a good source of calcium. • Soymilk: Soymilk is a high-quality source of soy protein that’s available in a variety. PBRC of 2005 forms, including chocolate. 4 of 28

Sources… • Isoflavone compounds, such as genistein and daidzein, are found in a number of plants, but soybeans and soy products like tofu and textured vegetable protein are the primary food sources. PBRC 2005 5 of 28

Food Serving Soy protein (g) Soy Burger 1 patty 8 7 100 Soy nuts 1 oz 12 38 150 Soy Milk 1 c 8 24 100 Texturized Vegetable Protein (TVP) ¼c 14 27 50 Tofu 3 oz 9 33 45 Soy Protein Bar 1 bar 6 10 -15 180 Soy Breakfast Patty 2 patties 16 4 160 Soy Flour ¼c 12 33 90 Soy Beans, Boiled ½c 7 47 190 Tempeh ½c 18 36 200 Soy Nut Butter 2 Tbs. PBRC 2005 8 Isoflavone content Kcal (mg) 0 6 of 28 160

Mechanisms of Action. . • There are many proposed mechanisms for therapeutic effect of isoflavones • The mechanisms include: – binding to estrogen receptors – inhibition of production of reactive oxygen species – induction of DNA strand breakage resulting in apoptosis or cell death – inhibition of angiogenesis – inhibition of thrombin formation and platelet activation – And increased LDL receptor activity PBRC 2005 7 of 28

Health Effects of Soy PBRC 2005 8

Estrogenic and Antiestrogenic Activity • Relative to physiologic estrogens, isoflavones appear to be a weaker form according to both in vitro and in vivo assays • Because of this, its believed that isoflavones can compete at estrogen receptor sites, blocking the stronger version naturally produced by the body from exerting its full effect • Since high blood levels of estrogen are an established risk factor for breast cancer, weaker forms of estrogen may provide protection against this disease PBRC 2005 9 of 28

Estrogenic and Antiestrogenic Activity • The prevailing hypothesis has been that isoflavones exert antiestrogenic effects when placed in a highestrogen environment, such as exists in premenopausal women, and estrogenic effects when in a low-estrogen environment, such as exists in postmenopausal women • There has been some support to this hypothesis, however definite conclusions regarding whether soy or isoflavones are necessarily antiestrogenic in premenopausal women is still currently a topic of much debate PBRC 2005 10 of 28

Breast Cancer • Interest in the relationship between soy intake and cancer risk was due, in large part, to the relatively low breast cancer mortality rates in Asian countries where soyfoods are commonly consumed • In Japan, the breast cancer mortality rate is about ¼ that of the United States PBRC 2005 11 of 28

Breast Cancer • Of the multitude of studies conducted outside the US on women, most find that there are decreases in breast cancer risk with consumption of soy products in premenopausal, but not postmenopausal women • The only case-controlled study conducted thus far in the United States to examine this possible relationship found that tofu consumption was protective in both premenopausal and postmenopausal Asian women • The downfall of this study was that it only included one particular group of women- whether or not this PBRC 2005 12 of 28 would be indicative of other women remains

Breast Cancer • Overall, the epidemiologic data are inconclusive • There is little epidemiologic support for the notion that soy intake is associated with a decreased risk of postmenopausal breast cancer • However, there is some data suggestive of decreased risk of premenopausal breast cancer with increased soy intakes PBRC 2005 13 of 28

Prostate Cancer • There is speculation that the intake of soyfoods may be a factor contributing to the low prostate cancer mortality rate in Japan • Although the data in support of this hypothesis is intriguing, it is also limiting • Genistein has shown to inhibit the growth of both androgen-dependent androgen-independent prostate cancer cells in vitro PBRC 2005 14 of 28

Other Mechanisms By which genistein or isoflavones could reduce prostate cancer risk • Even though the precise role of estrogen in prostate cancer is not well defined, the potential estrogenic effects of isoflavones may be protective because estrogens have been used successfully as a form of hormone therapy for metastatic prostate cancer PBRC 2005 15 of 28

Prostate Cancer • Human data available remains limited for use in evaluating the soy-prostate cancer hypothesis • Of potential relevance to the effects of isoflavones on prostate cancer risk is the finding that isoflavones appear in the prostatic fluid, and that concentrations are highest in men from soyfood-consuming countries • Furthermore, relative to plasma concentrations, isoflavones are concentrated several-fold in the prostatic fluid PBRC 2005 16 of 28

Soy and Bone Health • Speculation about the potential benefits of isoflavones was in part fueled by the similarity in chemical structure between the soybean isoflavones and the synthetic isoflavone, 7 -isopropoxyisoflavone, which was shown to increase bone mass in postmenopausal women PBRC 2005 17 of 28

Soy and Bone Health • Two human studies that examined the effects of soy consumption on bone mineral loss in postmenopausal women have been reported thus far • In both studies, soy was associated with favorable effects on bone density or content; however, the results are still considered preliminary PBRC 2005 18 of 28

Soy & Bone Health • Although the effects of soy and isoflavones on bone health constitutes and exciting area of research, no firm conclusions can be reached at this time • With the large number of studies currently underway in this area; however, a better understanding should be on its way soon PBRC 2005 19 of 28

Soy & Cardiovascular Health: An Overview • Dietary soy protein has been shown to have several beneficial effects on cardiovascular health • Best-documented effect is on plasma lipid and lipoprotein concentrations, with reductions of ~10% in LDL cholesterol and small increases in HDL cholesterol • Dietary soy protein improves flow-mediated arterial dilation • Soy isoflavone extracts improves systemic arterial compliance, an indicator of atherosclerosis extent PBRC 2005 20 of 28

Soy & Cardiovascular Health: Plasma lipids lipoproteins Plasma Lipidsand Lipoproteins • Effects of dietary soy protein in human subjects has shown reductions in LDL cholesterol of ~13%, reductions in plasma triglycerides of ~10%, and increases in HDL cholesterol of around 2% • These beneficial effects of soy protein on plasma lipoproteins culminated recently in the U. S. Food and Drug Administration’s approval of the health claim that: – “ 25 g of soy protein a day, as part of a diet low in saturated fat and cholesterol, may reduce the risk of heart disease” PBRC 2005 21 of 28

Soy & Cardiovascular Health: LDL Oxidation • Interest is increasing in the role of LDL particle oxidation on both atherogenesis and vascular function • In healthy subjects receiving supplementation, soy treatment significantly prolonged LDL oxidation by ~20 minutes • Based on the findings that estradiol fatty esters were incorporated into LDL, Helisten et al. described that because soy isoflavones are incorporated into LDL PBRC 2005 22 of 28 particles, it results in much greater oxidation

Soy & Cardiovascular Health: Arterial Function Endothelium-mediated vasodilation • Two approaches are used to evaluate endothelium-mediated vasodilation – One determines the response of arteries to the perfusion of acetylcholine – The other is flow-mediated dilation whereby flow is restricted • When genistein was infused it resulted in increased brachial artery dilation of both men and women comparable to 23 the PBRC 2005 of 28

Soy & Cardiovascular Health: Arterial Function Arterial Compliance Systole diastole • Unlike endothelial-mediated vasodilation (primarily nitric oxide dependent), arterial compliance relates to the constriction and dilation of arteries associated with systole and diastole • In humans, supplementation with soy protein or the administration of isoflavone extracts seems to improve arterial compliance PBRC 2005 24 of 28

Soy & Cardiovascular Health: Atherosclerosis • Currently, there is considerable literature establishing that substitution of animal protein (usually casein) with soy protein results in reduced amounts of atherosclerosis resulting from diets with added cholesterol • Current research is focusing primarily on identifying what components of soy protein provide this atherosclerosis protection PBRC 2005 25 of 28

Soy & Cardiovascular Health Atherosclerosis: Conclusions • Intact soy protein provides more cardiovascular benefits than does alcohol-washed soy protein • The addition of soy isoflavone extracts to diets containing animal protein or alcohol-washed soy protein does not provide plasma lipid concentration benefits • Lastly, soy isoflavone extracts given to human subjects do not result in cardiovascular benefits except for improvements in systemic arterial PBRC 2005 compliance 26 of 28

Conclusions… • Dietary soy intake seems to be promising in the areas of cardiovascular, cancer (especially prostate), and bone health • In time, soy’s roles and possibly emerging ones will be better understood PBRC 2005 27 of 28

References… • • • http: //nutrition. ucdavis. edu/infosheets/soy. htm http: //www. ajcn. org/cgi/content/full/70/3/439 S http: //www. nutrition. org/cgi/content/full/132/3/566 S http: //www. fwhc. org/health/soy. htm http: //www 3. cancer. gov/prevention/agents/Soy_Isofla vones. html • http: //www. thorne. com/altmedrev/. fulltext/3/5/376. pdf