Isoflavone Research Initiative

The safety of application and the benefits of isoflavones for postmenopausal women were the focus of a symposium organised by the CRN (Council for Responsible Nutrition), which took place on the 13^th and 14^th of May 2009 in Milan (Italy) under active participation of the EFSA (European Food Safety Authority).

Prof. Jin-Rong Zhou (Harvard Medical School, Boston) deepened the presentation of the animal models related to soy and cancer, with special attention to the question of a stimulation of cancer cell proliferation and the interaction between tamoxifen and isoflavones in cancer therapy (Zhou 2009), as postulated by the BfR (Anon. 2007). The typical model of xenotransplantation of MCF-7 cells to estrogen-depleted mice is a standard model in cancer research: It has been explicitly applied in the development of the cancer medication tamoxifen, an anti-estrogen (Gottardis et al. 1988). When isoflavones are tested the results vary, however, depending on the estrogen level. In estrogen-free mice a stimulation of cancer cell proliferation and an inhibition of tamoxifen effects are observed (Hsieh et al. 1998). Different results are, however, obtained when – as in menopausal women – there is still a residual quantity of estrogen circulating in the organism. In this case genistein even protects from cancer induction through estrogen, and it acts synergistically with tamoxifen (Mai et al. 2007).

After feeding mice with soy extract a dose-dependent protection from the formation of breast cancer was found (Zhou et al. 2004). This protection was not only expressed in a reduced growth rate of the cancer cells, but also in a positive influence on biological tumour markers for apoptosis and angiogenesis (Zhou et al. 2004). Genistein increased the effect of tamoxifen in mice already in low doses (Mai et al. 2007).

These examinations disprove the hypothetical potential of isoflavones to stimulate cancer cell growth. Interesting detail: When the variation of the animal models used by Helferich is applied to tamoxifen, the growth of breast cancer cells is also induced by this drug substance (Osborne et al. 1994), which is therapeutically used against cancer. From this model one would conclude on a carcinogenic effects of tamoxifen and not, as known, on the applicability of tamoxifen as an anti-estrogen against breast cancer. This again demonstrates the lack of relevance of the specific animal models used to prove the presumed cancer-promoting effects of isoflavones.

The limitation of Helferich’s animal model is clearly the complete absence of estrogen in the tissues – a situation which is not observed even in postmenopausal women. With more realistic conditions mimicking the hormonal conditions of the menopause the suspicion of cancer-promoting effects of isoflavones could long since be disproved.

Further reports from the Milan 2009 Soy Safety Symposium:

1. Plant “hormones”: Guilty by association with estrogens? International Symposium in Milan on the safety and efficacy of soy

2.  Facts Related to Bioavailability

3. Lack of relevance of animal models for an extrapolation of risks of isoflavones  

4. Isoflavones protect „menopausal” mice from breast cancer

5. Breast cancer risk is increased by synthetic gestagens

6. Breast tissue density remains unaltered with soy

7. Clinical studies demonstrate safety of soy in the breast

8. Study in more than 5,000 breast cancer patients: First positive tendencies with soy!

9. No effects of isoflavones on the endometrium

10. Isoflavones also safe at the thyroid gland

11. Backgrounds on Menopausal Hot Flushes

12. Clinical safety of isoflavone-containing preparations

13. Clinical effects of isoflavones against menopausal hot flushes

References

Anon. (2007). Isolierte Isoflavone in Nahrungsergänzungsmitteln und bilanzierten Diäten. Gesundheitliche Bewertung des BfR vom 30 11 2007.

Gottardis MM, Robinson SP and Jordan VC (1988). Estradiol-stimulated growth of MCF-7 tumors implanted in athymic mice: a model to study the tumoristatic action of tamoxifen. J Steroid Biochem 30(1-6):311-314.

Hsieh CY, Santell RC, Haslam SZ and Helferich WG (1998). Estrogenic effects of genistein on the growth of estrogen receptor-positive human breast cancer (MCF-7) cells in vitro and in vivo. Cancer Res 58(17):3833-3838.

Mai Z, Blackburn GL and Zhou JR (2007). Soy phytochemicals synergistically enhance the preventive effect of tamoxifen on the growth of estrogen-dependent human breast carcinoma in mice. Carcinogenesis 28(6):1217-1223.

Osborne CK, Jarman M, McCague R, Coronado EB, Hilsenbeck SG and Wakeling AE (1994). The importance of tamoxifen metabolism in tamoxifen-stimulated breast tumor growth. Cancer Chemother Pharmacol 34(2):89-95.

Zhou JR (2009). Soy, isoflavones, and mammary cancer: Overview of results from animal studies. Symposium on Evaluating the Efficacy and Safety of Isoflavones for Postmenopausal Women, 13-14 May. Milan (Italy): Council for Responsible Nutrition.

Zhou JR, Yu L, Mai Z and Blackburn GL (2004). Combined inhibition of estrogen-dependent human breast carcinoma by soy and tea bioactive components in mice. Int J Cancer 108(1):8-14.