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Soy Isoflavones

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					  Soy Isoflavones

Pennington Biomedical Research Center
         Division of Education
               Heli J. Roy PhD
              Shanna Lundy, BS
       Phillip Brantley, PhD, 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




                                                     Daidzein
         Genistein            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 of forms, including chocolate.
                           PBRC 2005                              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   Isoflavone content Kcal
                                     (g)              (mg)
   Soy Burger        1 patty           8               7                100
    Soy nuts          1 oz             12             38                150
    Soy Milk          1c               8              24                100
   Texturized         ¼c               14             27                50
Vegetable Protein
     (TVP)
      Tofu            3 oz             9              33                45
 Soy Protein Bar     1 bar             6             10-15              180
  Soy Breakfast     2 patties          16              4                160
      Patty
    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                160

                                PBRC 2005                     6 of 28
        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 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 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 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 would be
  indicative of other women remains unseen
                          PBRC 2005                           12 of 28
                      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 and 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 and lipoproteins
      Plasma lipids andLipoproteins
• 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 particles, it results in much
  greater oxidation resistance

                               PBRC 2005                         22 of 28
         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 2005                             23 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 compliance

                              PBRC 2005                        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/70/3/439S
•   http://www.nutrition.org/cgi/content/full/132/3/566S
•   http://www.fwhc.org/health/soy.htm
•   http://www3.cancer.gov/prevention/agents/Soy_Isoflavones.html
•   http://www.thorne.com/altmedrev/.fulltext/3/5/376.pdf

				
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