Soy beans, Soy Proteins and other Soy Products derived from beans contains six isoflavones.  The principal isoflavones are daidzein and genistein .Another isoflavone  glycitein is in minor amount.These are found in the form of glycosides.  Daidzin is 7-0-glucoside of daidzein, genistin is 7-0-glucoside of genistein while glycitin is 7-0-glucoside of glycitein.  All these O-glucosides may have malonyl or acetyl groups linked to hydroxyls of glucose units.  The major part of isoflavones is soy beans is present as glucosides (mainly as malonyl or acetyl glucosides).  In fact only 2 to 5% is present as aglycones – daidzein or genistein.  When soy products are consumed by humans, the isoflavone glycosides are degraded to aglycones, genistein or daidzein  which in turn degraded by gut microflora, pancreatic or intestinal enzymes to aglycones.  The isoflavone aglycones may be absorbed in intestines. Prior to absorption, the aglycones may be  partly transformed into p-ethyl phenol and 6'-hydroxy-O-desmethyl angolensin (transformed products from genistein) or equal while O-desmethylangolensin is a transformed product from daidzein .  However, the metabolism of glycitein is not well understood.

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                                  The absorption of the aglycone isoflavones at the intestinal mucosa  is largely by passive absorption via micelles, follow the same route as lipid soluble compounds.  Ultimately when the isoflavones are released into the blood, they are loosely bound to albumins and other proteins.  In the tissues these aglycone isoflavones exert diverse physiological effects.  For example, these isoflavones are conjugated to glucuronides or sulphates present in liver cells.  The conjugates are secreted into gall bladder and ultimately excreted into the bile in the small intestine.

                                 Isoflavones conjugates and then deconjugate by bacterial enzymes in the intestines resulting again reabsorption.  In the gut  these isoflavones will be bound to fiber and other molecules and excreted through faeces.  Isoflavones and their metabollites in the blood are finally excreted into the urine by the kindneys.

                     The main interest or physiological  function of isoflavones is as “estrogenic” compounds.  In fact these isoflavones along with natural  coumestans and lignans are termed as “phytoestrogens”.

                     In body, reproductive cells contain ten times more estrogen receptors than non-reproductive cells.  The cells containing estrogen receptors are influneced by isoflavones or its metabolites in blood.  It should be emphasised that estrogenic activity of these phytoestrogens (including isoflavones) is far less.  For example if the potency of natural estrogenic compound, estradiol, is 100, genistein has 0.40 potency, daidzein 0.027 and glycitein 0.028.

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                       The most important observation is depending upon the natural estradiol levels in an individual ,phytoestrogens may exert estrogenic or anti-estrogenic effects.  Since the estrogenic activity of the isoflavones is much low, the overall estrogenic effect will be low compared to estradiol.

                       In  post- menopausal women, the estradiol levels are low.  In such case the estrogenic isoflavones will restore the unbalanced estrogenic effect.  In other words the soy isoflavones balance the estrogen levels both when estradiol levels are high (as in the case of pre-menopause) and low (as in the case of post-menopause of women).

                             There are no side effects detected with increase uptake of  soy isoflavones, at least at doses similar to a traditional Asian diet.  Asian diet contains higher amount of soy compared to western diet.  No adverse effects are detected when soy protein containing 90 mg/day isoflavones is taken.

                              Clinical trials, that have been done so far, has not shown any adverse effects.  For clinical trials soy milk, soy flour, soy cake, tofu, soy, protein beverage, soy germ, tablets all containing isoflavones ranging from 25 mg-60 mg isoflavones were used and no adverse effect was detected.  Most of these preparations are available commercially in western countries.
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FURTHER TOXICOLOGICALSTUDIES REVEALED:
*  genistein and diadzein were not mutagenic in Ames test.
*  genistein inhibited thyroxine synthesis.
*   prolonged consumption of even more than 100 mg of isoflavones per day showed no adverse effects.

* High isoflavones in red clover when fed to sheep caused infertility to sheep.  In fact in Australia live stock developed infertility when they consumed red clover as feed.  This observation led to chemical investigation of red clover which led to the discovery of isoflavone, genistein.

     However, research point out that metabolic pathways of animals are very much different from human system.  Moreover Asians, who consume large amounts of soy, did not have reduced fertility. Therefore is no harm in consuming soy products for prolonged time and at higher amounts regularly.

     There is a booming interest in soy foods and supplements in  USA.  In USA, the preventive role of soy, in coronary heart diseases (CHD), Cancer, Osteoporosis and menopause is well publicised in media.

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     Some salient points on the virtues of soy, products containing isoflavones are

*  Soy proteins ability to lower serum cholesterol levels is well established..  Clinical studies revealed that 25 gm/day reduces total serum cholesterol (9.3%), LDL  cholesterol (12.9%) and triglycerides (10.5%).

     Soy,  after extracting isoflavones , does not show a significant cholesterol lowering effect.  Incidentally the isoflavones, isolated from Soy , also does not show significant cholesterol-lowering effect.

     Thus studied individually soy isoflavones or proteins without isoflavones showed no significant effect.  Therefore soy  isoflavones in combination with proteins is essential for decreasing the risk of CHD (Coronary  Heart Diseases)

*    Plaque formation in arterial walls is the result of LDL oxidation.  Soy isoflavones act as antioxidants by neutralising or slowing down the rate of oxidation of LDL cholesterol.

     One study revealed that esterification of isoflavones with long chain fatty acids increased the incorporation of the isoflavones in LDL particles, thus prolonging oxidative lag times and thereby decreasing the plaque formation.

Soy  and Cancer.
*     Soy is postulated to prevent cancer cell metastatis.

*  Genistein inhibits certain protein kinases which are responsible for
growth of cancer cells.  One hypothesis is that genistein stabilises DNA topoisomerase II to DNA.
 This implies that proliferating tumor cells are forced by genistein to undergo terminal differentiation and cease dividing.

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*   Another possible mechanism by which soy isoflavones prevent cancer is that isoflavones act as antioxidants, scavenging free radicals, inhibiting cancer cell metastatis by limiting cell growth or encouraging cell differentiation.

Soy and Menopause.

*    During menopause and  premenopause, there is a reduction in the circulating estrogen levels within the body.  This results in hot flashes, night sweats, headache, irritability and prone to risk for CHD and osteoporosis.

     Once again how soy, would alleviate menopausal symptoms or reduced the risk of cancer is, due to the role of soy isoflavones as weak estrogens.  These isoflavones compete with bodys’estrogen for binding sites on cells.   Isoflavones gets bound to reproductive cells, thus inhibiting over exposure to estrogen.

      During menopause or during periods of low estrogen flow, isoflavones regulate the other harmones (act as estrogen) to relieve menopausal symptoms.

                         As mentioned earlier,soy isoflavones and other phytoestrogens (for example coumesterol and lignans) have approximately 1000 times weaker than human estrogens (for example estradiol) . Isoflavones compete with estrogen to bind to cells tissue that has estrogen receptor sites and thereby decrease or prevent unwanted estrogen action.  Isoflavones are  selective estrogen receptor modulators and regulate estrogen activity (whether estrogen is low or high in the body) without resulting in the negative side effects characteristic of estrogen.

     * Harmone replacement therapy is recommended for women going through phase of menopause to prevent osteoporosis.  It is valid to presume that isoflavones being weak estrogens, can also prevent osteoporosis.

   * Clinical studies revealed the efficacy of a soy, isoflavone through soy dietary supplements, comparable with harmone replacement therapy.  A clinical study revealed that after that after ingesting 160mg of isoflavones for 6 weeks, six post menopausal women experienced similar biochemical changes such as bone metabolism – as those produced by  Harmone Replacement Theraphy (HRT) results.

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  *  Soy experts recommending 30 mg to 60 mg of isoflavones (in aglycone form) based on the estimated consumption of soy foods by Asians.     For  example if there 100 mg of isoflavones in a soy food, 60% that is 60 mg in aglycone form.  Aglycone form is the active form that body requires.

     Further research is necessary to explore the role of isoflavones in the prevention of several disease.  The biochemical and pharmacological studies on genistein and daidzein and their role in the prevention of the diseases given below on investigation by several research  workers

*   Coronary heart disease
*    Harmone replacement therapy during menopause and post menopause.
*    Osteoporosis
*    role as antioxidants
*    Diabetes
*    Cognition and Alzheimer’s disease
*    Cancer
*    Kidney diseases and Adipose tissue development. Of course soy is not a magic bullet and but it should be a regular dietary supplement with qnantified amount of isoflavone aglycones.

CHEMICAL AND BIOCHEMICAL STUDIES GENISTEIN AND DAIDZEIN AND RELATED ISOFLAVONES MAY BE REWARDING .
 

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Structures

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