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Committee on Hormonally Active Agents in the Environment Phytoestrogens "The recent practice of feeding infants soy-based formula has raised concerns with regard to the long-term health effects of exposure during development..." "The concentration of soy phytoestrogens that inhibited thyroid hormone biosynthesis is within the range of exposure of infants maintained on soy formula." "...exposure of plant estrogens found in wood..." Note that these are the same as those being added to margarines. Human and animal exposures to the phytoestrogens,
particularly isoflavones, can be very high, because these compounds
are found in many foods. Genistein,
daidzein, formononetin, and equol are all present in clover. Infertility in sheep, “clover disease”, has been
traced to isoflavone concentrations as high as 5% of the dried weight
of clover (Verdeal and Ryan 1979). The recent practice of feeding infants soy-based
formula has raised concerns with regard to the long-term health
effects of exposure during development (Setchell et al. 1997; Irvine
et al. 1998). For example,
it has been recognized for some time that feeding infants soy-based
formula was associated with goiter (thyroid enlargement associated
with thyroid hormone deficiency) in animals and human infants (Shepherd
et al. 1960). One mechanism
by which isoflavonoids, such as genistein, reduce thyroid hormone
concentrations and result in goiter is by inhibiting thyroid peroxidase
activity; this enzyme catalyzes thyroid hormone biosynthesis (Divi
and Doerge 1996). The
concentration of soy phytoestrogens that inhibited thyroid hormone
biosynthesis is within the range of exposure of infants maintained
on soy formula. Soy-based formulas contained isoflavones at 32-47mg/mL,
which corresponded to a daily exposure to total isoflavones of 4.5-8.0
mg/kg of body weight per day for a 4-mo-old infant.
That concentration is 6- to 11-fold higher than concentrations
known to cause hormonal effects in adults. (Divi et al. 1997; Setchell
et al. 1997). In a
study by Irvine et al. (1998), the phytoestrogen content of soy-based
formulas and cereals were compared with dairy-based formulas and
human breast milk. Again,
the infants received approximately 3 mg/kg of body weight per day
from the soy-based formula, but a single daily serving of infant
cereal could increase the isoflavone intake by more than 25%. Dairy-based formula and human breast milk contained isoflavones
below the limit of detection.
Human breast milk had undetectable concentrations of phytoestrogens
regardless of the diet of the mother, including women who were vegetarians
and consumed greater than 50 g of soy products in a 48-hr period
before sampling. Potential exposure to plant estrogens found in wood
has been assessed by various in vitro and in vivo bioassays. Wood-derived estrogens, such as beta-sitosterol, could represent
environmental hormone exposures, particularly from pulp and paper
mill effluents, downstream of wood-processing facilities, Mellanen
et al. (1996) used two breast-cancer cell lines in vitro (MCF7 and
T-47D) and expression of the vitellogenin gene in rainbow-trout
livers to estimate estrogenic activity of wood-derived compounds.
Some compounds, such as beta-sitosterol, were estrogenic
in human and fish bioassays, but some phytoestrogens, such as betulin
and pinosylvin were estrogenic only in humans.
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