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Publication # 18




 Soy
 Isoflavones
Heli J. Roy, PhD,
MBA, RD
Shanna Lundy, BS
Beth Kalicki, BS
Pennington Biomedical Research Center
Division of Education
Phillip Brantley, PhD, Director
Steven Heymsfield, MD,
Executive Director
www.pbrc.edu                  PBRC 2012
Introduction

 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 2012
Introduction
 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




                                                       PBRC 2012
     Genistein                                     Daidzein
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 of forms, including chocolate.
                                                                PBRC 2012
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 2012
Food            Serving     Soy protein    Isoflavone             Kcal
                                       (g)       content (mg)
    Soy Burger          1 patty         8             7                  100
     Soy nuts            1 oz          12             38                 150
      Soy Milk           1c             8             24                 100
Texturized Vegetable     ¼c            14             27                  50
   Protein (TVP)

       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.          8             0      PBRC 2012   160
Mechanisms of Action..

 There are many proposed mechanisms for the
  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 2012
Health Effects of Soy


                        PBRC 2012
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 2012
Estrogenic and Antiestrogenic Activity


   The prevailing hypothesis has been that isoflavones exert
    antiestrogenic effects when placed in a high-estrogen
    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 2012
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 soy foods are
  commonly consumed.

 In Japan, the breast cancer mortality rate is about ¼ that of
  the United States.


                                                       PBRC 2012
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 would be indicative of other
    women remains unseen                                       PBRC 2012
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 2012
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 and androgen-independent prostate cancer cells
    in vitro

                                                               PBRC 2012
Other Mechanisms

How 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 2012
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 soy food-consuming countries

   Furthermore, relative to plasma concentrations, isoflavones
    are concentrated several-fold in the prostatic fluid
                                                              PBRC 2012
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 2012
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 2012
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 2012
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 extract improves systemic arterial compliance, an
    indicator of atherosclerosis extent.
                                                                    PBRC 2012
Soy & Cardiovascular Health

Plasma lipids and 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 2012
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 particles, it results
    in much greater oxidation resistance
                                                                PBRC 2012
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 the effect of estradiol.
                                                                   PBRC 2012
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 2012
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 2012
Soy & Cardiovascular Health
                 Atherosclerosis: Conclusions
 Intactsoy 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 compliance .
                                                           PBRC 2012
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 2012
References…
 http://www.fwhc.org/health/soy.htm
 http://www.cancer.org/Search/index?QueryText=soy&x=0&y=0
 http://www.aicr.org/foods-that-fight-
  cancer/foodsthatfightcancer_soy.html?
  gclid=COuO9IOCmrICFcFgTAodUFsAxA
 http://jn.nutrition.org/content/132/3/566S.long
 http://www.fda.gov/food/labelingnutrition/labelclaims/healthclaim
  smeetingsignificantscientificagreementssa/default.htm
                                                       PBRC 2012
About Our Company…
The Pennington Biomedical Research Center is a world-renowned nutrition research center.
 
Mission:
To promote healthier lives through research and education in nutrition and preventive medicine.
 
The Pennington Center has several research areas, including:
 
Clinical Obesity Research
Experimental Obesity
Functional Foods
Health and Performance Enhancement
Nutrition and Chronic Diseases
Nutrition and the Brain
Dementia, Alzheimer’s and healthy aging
Diet, exercise, weight loss and weight loss maintenance
 
The research fostered in these areas can have a profound impact on healthy living and on the prevention of common
chronic diseases, such as heart disease, cancer, diabetes, hypertension and osteoporosis.
 
The Division of Education provides education and information to the scientific community and the public about research
findings, training programs and research areas, and coordinates educational events for the public on various health issues.
 
We invite people of all ages and backgrounds to participate in the exciting research studies being conducted at the
Pennington  Center in Baton Rouge, Louisiana. If you would like to take part, visit the clinical trials web page at
www.pbrc.edu or call (225) 763-3000.
                                                                                                       PBRC 2012

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Health benefits of soy isoflavones

  • 1. Publication # 18 Soy Isoflavones Heli J. Roy, PhD, MBA, RD Shanna Lundy, BS Beth Kalicki, BS Pennington Biomedical Research Center Division of Education Phillip Brantley, PhD, Director Steven Heymsfield, MD, Executive Director www.pbrc.edu PBRC 2012
  • 2. Introduction  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 2012
  • 3. Introduction  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 PBRC 2012 Genistein Daidzein
  • 4. 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 of forms, including chocolate. PBRC 2012
  • 5. 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 2012
  • 6. Food Serving Soy protein Isoflavone Kcal (g) content (mg) Soy Burger 1 patty 8 7 100 Soy nuts 1 oz 12 38 150 Soy Milk 1c 8 24 100 Texturized Vegetable ¼c 14 27 50 Protein (TVP) 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. 8 0 PBRC 2012 160
  • 7. Mechanisms of Action..  There are many proposed mechanisms for the 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 2012
  • 8. Health Effects of Soy PBRC 2012
  • 9. 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 2012
  • 10. Estrogenic and Antiestrogenic Activity  The prevailing hypothesis has been that isoflavones exert antiestrogenic effects when placed in a high-estrogen 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 2012
  • 11. 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 soy foods are commonly consumed.  In Japan, the breast cancer mortality rate is about ¼ that of the United States. PBRC 2012
  • 12. 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 would be indicative of other women remains unseen PBRC 2012
  • 13. 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 2012
  • 14. 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 and androgen-independent prostate cancer cells in vitro PBRC 2012
  • 15. Other Mechanisms How 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 2012
  • 16. 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 soy food-consuming countries  Furthermore, relative to plasma concentrations, isoflavones are concentrated several-fold in the prostatic fluid PBRC 2012
  • 17. 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 2012
  • 18. 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 2012
  • 19. 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 2012
  • 20. 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 extract improves systemic arterial compliance, an indicator of atherosclerosis extent. PBRC 2012
  • 21. Soy & Cardiovascular Health Plasma lipids and 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 2012
  • 22. 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 particles, it results in much greater oxidation resistance PBRC 2012
  • 23. 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 the effect of estradiol. PBRC 2012
  • 24. 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 2012
  • 25. 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 2012
  • 26. Soy & Cardiovascular Health Atherosclerosis: Conclusions  Intactsoy 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 compliance . PBRC 2012
  • 27. 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 2012
  • 28. References…  http://www.fwhc.org/health/soy.htm  http://www.cancer.org/Search/index?QueryText=soy&x=0&y=0  http://www.aicr.org/foods-that-fight- cancer/foodsthatfightcancer_soy.html? gclid=COuO9IOCmrICFcFgTAodUFsAxA  http://jn.nutrition.org/content/132/3/566S.long  http://www.fda.gov/food/labelingnutrition/labelclaims/healthclaim smeetingsignificantscientificagreementssa/default.htm PBRC 2012
  • 29. About Our Company… The Pennington Biomedical Research Center is a world-renowned nutrition research center.   Mission: To promote healthier lives through research and education in nutrition and preventive medicine.   The Pennington Center has several research areas, including:   Clinical Obesity Research Experimental Obesity Functional Foods Health and Performance Enhancement Nutrition and Chronic Diseases Nutrition and the Brain Dementia, Alzheimer’s and healthy aging Diet, exercise, weight loss and weight loss maintenance   The research fostered in these areas can have a profound impact on healthy living and on the prevention of common chronic diseases, such as heart disease, cancer, diabetes, hypertension and osteoporosis.   The Division of Education provides education and information to the scientific community and the public about research findings, training programs and research areas, and coordinates educational events for the public on various health issues.   We invite people of all ages and backgrounds to participate in the exciting research studies being conducted at the Pennington  Center in Baton Rouge, Louisiana. If you would like to take part, visit the clinical trials web page at www.pbrc.edu or call (225) 763-3000. PBRC 2012