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SECOND INTERNATIONAL SYMPOSIUM
ON THE ROLE OF SOY
IN PREVENTING AND TREATING CHRONIC DISEASESeptember 15-18, 1996
Brussells, Belgium
SCIENTIFIC PROGRAM
Satellite Symposium
Current Understanding of Soy and Infant Health
Isoflavone Content of Infant Formula and the Metabolic Fate of These Phytoestrogens
Kenneth D. Setchell.
Clinical Mass Spectrometry Center, Children's Hospital Medical Center, Cincinnati, OhioInterestingly, more than a decade after first drawing attention to the fact that soy infant formulas contain significant levels of isoflavones (Setchell 1985; Setchell et.al. 1987a), concerns have recently been expressed about the possible implications for the infant of isoflavone intake from infant formulas (Irvine et.al. 1995). While there is little evidence to suggest that ingestion of isoflavones, at levels consistent with amounts present in soy protein foods (0.1-4.0 mg/g; Coward et.al. 1993) has any adverse effects in adults or infants, the potential role these compounds may play in creating steroid hormone imbalance, or their competition for the normal steroid, drug and xenobiotic metabolizing enzymes is presently unknown. These concerns are fueled by the known adverse effects in several animal species following the ingestion of relatively high concentrations of dietary estrogens (Bennetts et.al. 1946; Setchell et.al. 1987b), and our more recent studies which demonstrate that a diet containing soy protein causes a prolongation of the length of the menstrual cycle and a suppression of the usual mid-cycle surge in pituitary gonadotrophins (Cassidy et.al. 1994). Furthermore, the hypocholesterolemic action of soy protein has been known for some time and is well established (Anderson et.al 1995). These observations are consistent with hormonal actions and do not occur in the absence of isoflavones (Cassidy et.al. 1995). These physiological effects asre not surprising given the very high circulating plasma concentrations of isoflavones (range 100-800 ng/ml) that are attained relative to plasma estradiol concentrations (30-60 pg/ml) after ingestion of modest amounts of soy protein foods (Setchell 1995).
There appears to be considerable confusion, and data are scant relating to the composition and metabolic fate of isoflavones in the infant. While ethical considerations make it difficult to obtain accurate data in early life, our studies indicate that all soy infant formulas contain isoflavones (Setchell et.al. 1987a), and although the total concentrations are relatively low when expressed on a per mL basis, it should be realized that the average intake of soy milk by a 4 month-old infant (900-1000 mL) provides a daily intake of isoflavones of 15-35 mg, which is equivalent to 2.0-4.4 mg/kg body weight. This compares with an intake of 0.7-2.1 mg/kg body weight for most adults consuming soyfoods containing between 50-150 mg. Our studies indicate that infants fed soy infant formulas absorb the isoflavones, as evidenced from the high but variable urinary concentrations (Cruz et.al. 1994). Based on semi-quantitative assessments, the concentrations of daidzein and genistein in urine are lower than in adults consuming lesser quantities of isoflavones (Setchell et.al. 1984), suggesting that the bioavailability of dietary isoflavones in the infant is lower than in adults. This may be partly explained by the lack of a fully developed microflora in early life, or inactivity of the key enzymes necessary for initiating intestinal metabolism of the glycosidic conjugates of isoflavones in soy milk formulas (Cruz et.al 1994).
It has been recently claimed that human milk is a useful source of phytoestrogens (Slavin 1996), however, our data do not support this view. Phytoestrogen concentrations in human milk measured by gas chromatography-mass spectrometry were found to be <5 ng/mL and although they increase up to 10-fold when the lactating mother consumes soy foods, the contribution of phytoestrogen intake from human milk is relatively small and insignificant when compared with the levels attained from soy infant formulas. These findings are confirmed by others (Franke & Custer 1996). Overall intake of phytoestrogens through human milk, based on concentrations ranging 5-20 ng/mL is estimated to be about 1/3000th that of soymilk formulas. Furthermore, isoflavones are predominantly found as glucuronide conjugates in human milk, while they are present mainly as various forms of glycosidic conjugates in soymilk (Coward et.al. 1993). These compositional differences may influence their bioavailability. Our earlier findings clearly indicate that the glycosidic conjugates in soy milk formulas are readily hydrolyzable by intestinal glucosidases, which release the bioactive aglycones making them available for absorption and urinary excretion (Cruz, et.al. 1994).
The available data indicates that there is little reason to be concerned about the maternal-infant transfer of phyutoestrogens from human breast milk to the infant. Given the weak estrogenic activityof these compounds relative to endogenous estrogens (Setchell & Adlercreutz 1988), it is doubtful that the levels found in human milk are sufficient to exert any significant biological effects. Nevertheless, it is unequivocal that all soy infant formulas contain sufficiently high levels of isoflavones to yield comparable urinary and plasma concentrations of isoflavones in infants to those observed for adults consuming soy protein foods. For this reason, questions concerning the possibility for adverse effects have been raised. While there are theoretical possibilities for potential adverse effects of exposure to high levels of dietary estrogens (Mori & Nagasawa 1988), practical examples to support these concepts have yet to be definitively established in humans. This may be because it is not possible to consume large enough amounts of soy foods to reach toxicological levels of these compounds to induce the type of pathological effects seen in animals. This situation however may change with the recent introduction of commercial OTC soy isoflavone supplements, and the potential for self-induced mega-dosing with these products should be a serious concern for the future.
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