Nexus - 0706 - New Times Magazine-pages

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deBriefings risk factor for a number of estrogen-associated diseases. menstrual cycle length (Cassidy et al., 1994), it is unclear Even without the evidence of elevated serum estradiol levels whether the soy effects are beneficial or adverse. Furthermore, in rhesus fetuses, potency and dose differences between DES we need to be concerned about transplacental passage of and the soy isoflavones do not provide any assurance that the _ isoflavones, as the DES case has shown us that estrogens can soy protein isoflavones per se will be without adverse effects. pass the placenta. No such studies have been conducted with First, calculations based on the literature show that doses of genistein in humans or primates. As all estrogens which have soy protein isoflavones used in clinical trials which demon- ___ been studied carefully in human populations are two-edged strated estrogenic effects were as potent as low but active doses swords in humans (Sheehan and Medlock, 1995; Sheehan, of DES in rhesus monkeys (Sheehan, unpublished data). 1997), with both beneficial and adverse effects resulting from Second, we have recently shown that estradiol shows no _ the administration of the same estrogen, it is likely that the same threshold in an extremely large dose-response experiment characteristic is shared by the isoflavones. The animal data is (Sheehan et al., 1999), and we subsequently have found 31 also consistent with adverse effects in humans. dose-response curves for hormone-mimicking chemicals that Finally, initial data from a robust (7,000 men), long-term also fail to show a threshold (Sheehan, (30+ years) prospective epidemiological 1998a). Our conclusions are that no dose study in Hawaii showed that Alzheimer's is without risk; the extent of risk is simply a disease prevalence in Hawaiian men was function of dose. These two features sup- similar to European-ancestry Americans port and extend the conclusion that it is and to Japanese (White et al., 1996a). In reer eallow heal ces or | Subsequently on eee eee ent ar Additionally, isoflavones are inhibitors this same group higher than in European-ancestry and Ta” Inhibition can be expected to | SHOWed a significant root or environmental factors In apan generate thyroid abnormalities, including dose-dependent risk and Hawaii are responsible for the higher goiter and autoimmune thyroiditis. There . prevalence of vascular dementia in these exists a significant body of animal data (up to 2.4 fold) locations. Subsequently, this same group that demonstrates goitrogenic and even for development of showed a significant dose-dependent risk carcinogenic effects of soy products . (up to 2.4-fold) for development of (Kimura et al., 1976). Moreover, vascular dementia and vascular dementia and brain atrophy there are significant reports of goitro- brain atrophy from from consumption of tofu, a soy genic effects from soy consumption . product rich in isoflavones (White et in human infants (Van Wyk et al., consumption of tofu, al., 1996b). This finding is consistent a soy product rich in isoflavones. 1959; Hydovitz, 1960; Shepard et al., with the environmental causation 1960; Pinchers et al., 1965; Chorazy suggested from the earlier analysis, et al., 1995) and adults (McCarrison, and provides evidence that soy (tofu) 1933; Ishizuki et al., 1991). phytoestrogens cause vascular Recently, we have identified genis- dementia. Given that estrogens are tein and daidzein as the goitrogenic important for maintenance of brain isoflavonoid components of soy and function in women, that the male defined the mechanisms for inhibi- brain contains aromatase, the enzyme tion of thyroid peroxidase (TPO)-cat- that converts testosterone to estradiol, alyzed thyroid hormone synthesis in and that isoflavones inhibit this vitro (Divi et al., 1997; Divi et al., 1996). The observed suicide enzymatic activity (Irvine, 1998), there is a mechanistic basis inactivation of TPO by isoflavones, through covalent binding to —_ for the human findings. Given the great difficulty in discerning TPO, raises the possibility of neoantigen formation and __ the relationship between exposures and long-latency adverse because anti-TPO is the principal autoantibody present in _ effects in the human population (Sheehan, 1998b) and the autoimmune thyroid disease. This hypothetical mechanism is potential mechanistic explanation for the epidemiological consistent with the reports of Fort et al. (1986, 1990) of adou- _ findings, this is an important study. It is one of the more bling of risk for autoimmune thyroiditis in children who had robust, well-designed prospective epidemiological studies received soy formulas as infants compared to infants receiving generally available. We rarely have such power in human other forms of milk. studies, as well as a potential mechanism, and thus the results The serum levels of isoflavones in infants receiving soy should be interpreted in this context. formula are about five times higher than in women receiving Does the Asian experience provide us with reassurance that soy supplements who show menstrual cycle disturbances isoflavones are safe? A review of several examples led to the including an increased estradiol level in the follicular phase conclusion, "Given the parallels with herbal medicines with (Setchell, et al., 1997). Assuming a dose-dependent risk, it is respect to attitudes, monitoring deficiencies and the general unreasonable to assert that the infant findings are irrelevant to _ difficulty of detecting toxicities with long latencies, | am adults who may consume smaller amounts of isoflavones. unconvinced that the long history of apparent safe use of soy Additionally, while there is an unambiguous biological effect on products can provide confidence that they are indeed without this same group showed a significant dose-dependent risk (up to 2.4-fold) for development of vascular dementia and brain atrophy from consumption of tofu, a soy product rich in isoflavones. 12 - NEXUS Subsequently, OCTOBER —- NOVEMBER 2000