Narula-Soy Isoflavones SO

Narula Research
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by Acharan Narula, Ph.D., edited by Subhuti Dharmananda, Ph.D.


Studies in humans reveal that soy isoflavones can play a role in the prevention of hot flashes and menopausal symptoms (1). The isoflavones inhibit osteoporosis: the soy isoflavone daidzein is the biologically active metabolite of ipriflavone, a substance which has been available for the treatment of osteoporosis in 21 countries since 1989 (2). Soy supplementation is not associated, however, with the full spectrum of estrogenic effects in women (3); for example, it does not appear to stimulate estrogen-dependent breast tumors. It has been postulated that this apparent contradiction may arise from different binding capabilities or different primary binding sites for phytoestrogens compared to estrogen. In rat tissues, the isoflavones tend to bind more strongly to estrogen receptor beta (ER-b), while it is estrogen receptor alpha (ER-a) that estrogen binds to in producing several estrogenic effects; breast tissue is mainly supplied with ER-a receptors; there is only weak expression of ER-b in human breast tumor cells (4).


Soy protein lowers high cholesterol in humans (5, 6). The soy isoflavone genistein has a number of properties that suggest its potential as an anti-atherogenic agent. The progression of atherosclerotic lesions depends upon lipid peroxidation, especially that of LDL (low density lipoprotein; a carrier of cholesterol). At a dose of about 60 mg soy isoflavones per day for just two weeks, LDL develops considerable resistance to oxidation (7). Other factors leading to atherosclerosis include thrombin-induced platelet activation, proliferation of the smooth-muscle cells, expression of leukocyte adhesion molecules (b-integrins), and tyrosine kinase activation induced by growth factors (e.g., platelet-derived growth factor and basic fibroblast growth factor). Since genistein is a potent in vitro inhibitor of tyrosine kinase, and several of these other targets, this may account for a lower incidence of heart disease among populations consuming soy products (8).


The soy isoflavones inhibit cancer (9). Genistein can:

  1. induce cell-cycle arrest in leukemic cells (10);
  2. induce apoptosis in prostate cancer cells (11);
  3. inhibit the growth of cells from solid pediatric tumors, such as neuroblastomas (with both normal and enhanced MYCN oncogene expression), rhabdomyosarcoma, and Ewing’s sarcoma (12);
  4. inhibit both estrogen-stimulated and growth-factor stimulated proliferation of human breast cancer cells (13);
  5. suppress the expression of stress-response related genes (14).

Genistein can inhibit the growth of both human and rodent cancer cell lines (15): breast, prostate, and colon. Proposed mechanisms include (16):

  1. anti-estrogenic effects;
  2. induction of cancer cell differentiation, inhibition of tyrosine kinase and DNA topoisomerase-II activities;
  3. suppression of angiogenesis (see below); and
  4. anti-oxidant effects.

There is a substantial reduction in breast cancer risk among women with a high intake of phytoestrogens, particularly isoflavones (17). In premenopausal women with regular ovulatory cycles, 45 mg of soy isoflavones given daily for one month significantly suppressed the mid-cycle surges of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and increased the follicular phase length and/or delayed menstruation: such an effect is considered beneficial wtih respect to risk of breast cancer. Genestein and daidzen may regulate the levels of estrogen and testosterone by inhibiting steroid biosynthesis enzymes, thus reducing risk of breast and prostate cancer (18). According to a study of soy isoflavone effects, it has been proposed (19) that for significant anticarcinogenic effects, the dosage of the isoflavones should be about 1.5–2.0 mg/kg per day (for a 70 kg body weight, this is 105–140 mg). Phytate, a soy component as well as a mammalian cell component, shows in vivo and in vitro anti-oxidant and anti-cancer action (20). Soy saponins inhibit colon cancer (induced by azoxymethane) in experimental animals (21).


Genistein is a strong inhibitor of in vitro angiogenesis (22). Pathological angiogenesis is an essential component of many diseases, such as rheumatoid arthritis, psoriasis, solid tumors, hemangiomas, diabetic retinopathy, blindness, and chronic inflammation (23). Without angiogenesis, solid tumors (both sarcomas and carcinomas) cannot grow beyond microscopic sizes, and will remain dormant, or even regress. An anti-angiogenic therapy can be expected to remain free from developing drug-resistance (24), unlike some cytotoxic cancer therapies.


Genistein inhibits the production of interleukin 8 (IL-8) in human gastric epithelial cells when stimulated by Helicobacter pylori, the bacterium species which is the major cause of chronic type-B gastritis and is strongly associated with both duodenal and gastric ulcerations, as well as MALT lymphoma. The gastric mucosa, once infected with Helicobacter pylori, are infiltrated with inflammatory cells, including neutrophil polymorphs and T-lymphocytes. IL-8 is a potent chemoattractant and activator of the inflammatory cells, and is one of the key molecules that is responsible for the initiation of acute inflammation and some endocrine abnormalities. Production of IL-8 at mucosal surfaces has been reported in respiratory, urogenital, vascular, and colonic epithelium, and it greatly contributes to mucosal inflammation (25). It is possible that IL-8 contributes to the so-called “leaky gut syndrome.”


A high phytate diet can effectively treat hypercalciuria and kidney stones in humans (26).


It is well known that daily consumption of soy-based ingredients (with ~20–80 mg of soy isoflavones) is both safe and widespread among Asian populations (16, 27). Individuals having a known allergy to soy protein or those who have a phenylalanine metabolic disorder (i.e., phenylketouria) should not use Nutra-Soy or other soy protein products. High levels of soy isoflavones can inhibit thyroid hormone synthesis by competing for the plasma iodine used in their production, which is sometimes notable in infants consuming soy milk as replacement for human or cow milk (28); this inhibitory effect, seen with many bioflavonoids, can be counteracted by assuring adequate levels of iodine in the diet.


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  2. Calcified Tissue International 1997; 61: S3–S35.
  3. Journal of Clinical Endocrinology and Metabolism 1995; 80(5): 1685–1690.
  4. Lancet 1997; 350: 971–972.
  5. New England Journal of Medicine 1995; 333: 276–282.
  6. Metabolism 1997; 46(6): 698–705.
  7. Proceedings National Academy of Sciences USA, 1998: 3106–3111.
  8. Biochemical Society Transactions 1997; 25: 31–32
  9. Journal of the National Cancer Institute 1991; 83:541–546.
  10. Leukemia 1993; 7(12): 2012–18.
  11. Molecular Pharmacology 1997; 51: 193–200
  12. European Journal of Clinical Investigation 1992; 22: 260–264
  13. Cell Growth and Differentation 1996; 7: 1345–1351.
  14. Journal of the National Cancer Institute 1998; 90:381–388.
  15. Environmental Health Perspectives 1995; 103 (Supplement 7): 103–112.
  16. Journal of Cellular Biochemistry Suppl. 1995; 22:181–187.
  17. Lancet 1997; 350; 990–994.
  18. American Journal of Clinical Nutrition 1994; 60:333–334.
  19. Journal of Nutrition 1994; 124:1789S–1792S.
  20. Life Sciences 1997; 61:343–354
  21. Nutrition and Cancer 1997; 27(2): 206–209.
  22. Journal of Nutrition 1995; 125:790S–797S.
  23. FASEB Journal 1997; 11:457–465.
  24. Nature 1997; 390:335–336 and 404–407.
  25. Cytokines 1997; 9(7): 514–520.
  26. Free Radical Biology and Medicine 1990; 8: 61–69
  27. Nutrition and Cancer 1994; 21:113–31.
  28. Biochemical Pharmacology 1997; 54(10): 1087–1096.



General References

Annals of Medicine 1997; 29: 95–120.

Annual Reviews of Nutrition 1997; 17: 353–81.

Journal of Cellular Biochemistry Supplement 1996; 26S:114–126.