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. Jeffrey Tice from the University of California in San Francisco reported on the results of a systematic evaluation of published data from randomized clinical trials on the effects of soy preparations, red clover and isolated isoflavones on breast tissue density (Tice 2009). Breast tissue density increases with the application of estrogen-gestagen combinations (Conner et al. 2008), and is decreased under tamoxifen therapy (Decensi et al. 2009; Meggiorini et al. 2008). It is also naturally decreasing in menopause (Kelemen et al. 2008).

In hormone therapy studies a slight decrease of breast tissue density is observed with placebo, an insignificant increase with estrogen, and a distinct increase with the combination from estrogen and gestagen (Conner et al. 2008). The latter also correlates with the increase in breast cancer rate. Regarding the isoflavones the working group of Prof. Tice identified seven randomized trials giving details on the effects of isoflavone intake on breast tissue density, with a total of 1602 women and study durations of up to three years (Atkinson et al. 2004; Marini et al. 2008; Maskarinec et al. 2003; Maskarinec et al. 2009; Powles et al. 2008; Verheus et al. 2008). Daily isoflavone doses ranged from 40 to 120 mg. In none of the studies an increase of breast tissue density was found under the impact of isoflavones. Tice pointed to the fact that an increase of breast tissue density counts as an unequivocal parameter for estrogenic effects. Therefore other, non-estrogenic mechanism would have to be made responsible if in fact an increased rate of breast cancer were observed with isoflavones – an observation which was, however, not made clinically.

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

Atkinson C, Warren RM, Sala E, Dowsett M, Dunning AM, Healey CS, Runswick S, Day NE and Bingham SA (2004). Red-clover-derived isoflavones and mammographic breast density: a double-blind, randomized, placebo-controlled trial [ISRCTN42940165]. Breast Cancer Res 6(3):R170-R179.

Conner P, Lundström E and von Schoultz B (2008). Breast cancer and hormonal therapy. Clin Obstet Gynecol 51(3):592-606.

Decensi A, Robertson C, Guerrieri-Gonzaga A, Serrano D, Cazzaniga M, Mora S, Gulisano M, Johansson H, Galimberti V, Cassano E, Moroni SM, Formelli F, Lien EA, Pelosi G, Johnson KA and Bonanni B (2009). Randomized Double-Blind 2 x 2 Trial of Low-Dose Tamoxifen and Fenretinide for Breast Cancer Prevention in High-Risk Premenopausal Women. J Clin Oncol 27(23):3749-3756.

Kelemen LE, Pankratz VS, Sellers TA, Brandt KR, Wang A, Janney C, Fredericksen ZS, Cerhan JR and Vachon CM (2008). Age-specific trends in mammographic density: the Minnesota Breast Cancer Family Study. Am J Epidemiol 167(9):1027-1036.

Marini H, Bitto A, Altavilla D, Burnett BP, Polito F, Di Stefano, V, Minutoli L, Atteritano M, Levy RM, D'Anna R, Frisina N, Mazzaferro S, Cancellieri F, Cannata ML, Corrado F, Frisina A, Adamo V, Lubrano C, Sansotta C, Marini R, Adamo EB and Squadrito F (2008). Breast Safety and efficacy of genistein aglycone for post-menopausal bone loss: A follow-up study. J Clin Endocrinol Metab 93(12):7487-7496.

Maskarinec G, Verheus M, Steinberg FM, Amato P, Cramer MK, Lewis RD, Murray MJ, Young RL and Wong WW (2009). Various Doses of Soy Isoflavones Do Not Modify Mammographic Density in Postmenopausal Women. J Nutr 139:981-986.

Maskarinec G, Williams AE and Carlin L (2003). Mammographic densities in a one-year isoflavone intervention. Eur J Cancer Prev 12(2):165-169.

Meggiorini ML, Labi L, Vestri AR, Porfiri LM, Savelli S and De Felice C (2008). Tamoxifen in women with breast cancer and mammographic density. Eur J Gynaecol Oncol 29(6):598-601.

Powles TJ, Howell A, Evans DG, McCloskey EV, Ashley S, Greenhalgh R, Affen J, Flook LA and Tidy A (2008). Red clover isoflavones are safe and well tolerated in women with a family history of breast cancer. Menopause Int 14(1):6-12.

Tice JA (2009). Effects of isoflavones on mammographic breast density in pre- and postmenopausal women. Symposium on Evaluating the Efficacy and Safety of Isoflavones for Postmenopausal Women, 13-14 May. Milan (Italy): Council for Responsible Nutrition.

Verheus M, van Gils CH, Kreijkamp-Kaspers S, Kok L, Peeters PH, Grobbee DE and van der Schouw YT (2008). Soy protein containing isoflavones and mammographic density in a randomized controlled trial in postmenopausal women. Cancer Epidemiol Biomarkers Prev 17(10):2632-2638.