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 13th and 14th of May 2009 in Milan (Italy) under active participation of the EFSA (European Food Safety Authority).
Early-on epidemiological studies have found a very low incidence rate of breast cancer in countries with a high consumption of soy (Lee et al. 1991; Wu et al. 1996). According to Prof. Mark Messina (Loma Linda University, USA) (Messina 2009) the isoflavones in soy have been made responsible for this effect (Messina et al. 2006). Genetic differences between populations of Asian countries and Western states with dietary habits low in soy could be excluded in migrant studies (Korde et al. 2009). In addition, the “Westernization” of dietary habits and the turning away from soy consumption in Japan – a country with an originally extremely low incidence rate of breast cancer – led to a strong, 3 to 4-fold increase of breast cancer incidence (Hirose et al. 2007; Ishimoto et al. 1994). However, an exposure to isoflavones in young age is possibly necessary to produce a lasting and distinct protective effect against breast cancer (Messina et al. 2009).
Whereas this protective effect by soy-rich nutrition is largely undisputed, the BfR hypothesized that breast cancer might be induced in women with an increased risk upon exposure to isoflavones (Anon. 2007). This is indicated by experimental models in rats to which dormant human breast cancer cells were transplanted (Allred et al. 2001a). The untimely activation of these breast cancer cells by estrogen is prevented by surgical removal of the ovaries. In such models high doses of genistein (750 ppm!) as well as estradiol stimulate cancer cell proliferation, whereas daidzein and equol do not have this effect (Allred et al. 2001b; Ju et al. 2006).
At the first glance this might be considered alarming. The model does, however, not reflect the conditions of the human organism. The animals do, for example, not possess a working immune system (Messina et al. 2008). In addition, the estrogen level of breast tissue is only marginally decreased even when the blood estrogen levels are very low, as in menopause (Simpson 2000) and under treatment with tamoxifen (Pearson et al. 1982). The situation of an absolute absence of estrogen, which is created in the animal model, does not occur in humans – the unphysiologically high doses of isoflavones not withstanding: 750 ppm in mice correspond to approximately 75 mg/kg, whereas safety studies in Italian women applied 54 mg/day (Marini et al. 2008), corresponding to 0.83 mg/kg. Even after application of the usual correction factors the dosage in the animal experiment was still seven times higher than in the human studies. In addition, genistein was a potent inhibitor of cancer recurrence after surgical removal of breast cancer and other cancer types in other experiments (Vantyghem et al. 2005).
The US-American group around Prof. Helferich concluded from their experiments in immunosuppressed rats with xenotransplanted human breast cancer a more potent stimulation of cancer cell proliferation the more processed the applied soy preparations were: Whereas soy flour as such did not cause the effect, an increasing rate of stimulation of cancer cell proliferation was postulated in the sequence from soy molasses over soy extracts down to isolated soy isoflavones (Allred et al. 2004; Helferich et al. 2008). Correspondingly, one of the conclusions drawn by the BfR from the works of Helferich was that soy food as such should not pose a problem, but that extracts and isolates are to be avoided, as obviously the cancer risk correlated with the higher intake of genistein (Anon. 2007). In studies on the absorption of genistein from different sources it has been amply documented that this hypothesis cannot be correct. Serum levels achieved with isolated genistein are not higher than those after consumption of soy food (Gardner et al. 2009). Other than in the models in mice the mechanisms of absorption prevent an accumulation of genistein in the human bloodstream. In addition, the idea of natural food and artificial extracts does not correspond to reality. In the contrary soy food such as tofu is highly processed, and has exactly the same profile of isoflavones as the rebuked extracts (Anon. 2008). Tofu is, however recognized as a food with cancer-protective properties (Kim et al. 2008; Wu et al. 1996). With the meanwhile available data on long-term safety of isoflavones in humans (Marini et al. 2008; Maskarinec et al. 2009). Dr. Messina considers the controversy around soy as solved – with a clear recommendation in favour of isoflavones.
Further reports from the Milan 2009 Soy Safety Symposium:
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.
Messina M (2009). Isoflavones and breast cancer: What is the basis for concern? Symposium on Evaluating the Efficacy and Safety of Isoflavones for Postmenopausal Women, 13-14 May. Milan (Italy): Council for Responsible Nutrition.
Cancer 