Establishing appropriate intake levels for isoflavones

Data on safety have been obtained from in vitro as well as in vivo animal and human studies (see also Section 10.4). About 50 years ago, Australian farmers observed an infertility syndrome in sheep associated with the consumption of clover species (Bennets et al., 1946). The clover compounds shown to cause the infertility (genistein, daidzein, equol, biochanin A, formononetin) were members of the isoflavone family (Bradbury and White, 1951 Shutt and Braden, 1968), raising the question of whether soy might cause infertility in humans (see also Section 10.4.9). A variety of reports further supported adverse effects of isoflavones on animal reproductive systems (Santell et al., 1997 Flynn et al., 2000a,b). 

Many clinical studies have been performed on human subjects to assess the effect of soy isoflavones on chronic disease risk factors with no ill-effects (see Section 10.4). The safety profile of isoflavones is, however, difficult to establish because of the limited sample sizes and short periods of investigation of such studies. At present the upper tested limits are  

For long-term exposure, questions have been raised on proliferative effects of breast duct epithelial cells in premenopausal women (Messina and Loprinzi, 2001, and refs therein). 

2 Phytoestrogen levels associated with health benefits 

Such evidence indicates that it might be unnecessary to reach the same intake of soy products as Japanese or other Asian populations to reach the same plasma levels of isoflavones. The rationale for such a difference could be a different bioavailability of the ingested isoflavones. Indeed, in most Asians a deficiency of an intestinal lactase, responsible for P-glucosides hydrolysis, might explain the lower isoflavones concentrations in the blood of the Japanese (Day et ai, 2000). 

---