et al. add fuel to growing concern about the safety of
soy-based infant formula, showing that exposure to genistein
(a phytoestrogen in soy) causes changes in the immune system of
exposed mice in ways that are consistent with observed reductions
in immune system efficiency in formula-fed infants. Moreover,
the amount of genistein necessary to cause effects in mice are significantly
below those that human infants experience when fed soy-formula.
has already banned the use of soy-based infant formula except under
medical conditions when other options are unavailable. This new
evidence form Yellayi et al., added to recent
research showing that genistein also induces uterine cancers
in mice as consistently as diethylstilbestrol (DES), makes it imperative
for FDA to revisit U.S. standards for infant formula.
did they do? In a series of experiments, Yellayi et al.
exposed juvenile and adult mice to genistein at various doses, and
then measured the impact of exposure on a different indicators of
immune system function. Their experiments also included procedures
to determine whether the use of injections (as opposed to ingestion)
might give misleading results, and whether the doses they used were
relevant to exposures experienced by infants consuming soy-based
did they find? In one set of experiments, Yellali et al.
injected adult mice with different levels of genistein and measured
changes in the weight of a gland important to the immune system,
the thymus. They found that higher levels of genistein repressed
injected into adult mice reduces thymus weight in a dose-dependent
manner, as does estradiol (E2), the positive control. An estrogen-blocker,
ICI, reverses the effect of E2 but but does not eliminate
altogether the effect of genistein, indicating that some but
not all of genistein's effect is mediated by the estrogen
Yellai et al. 2002
increased the rate of cell death (apoptosis) of thymocytes (cells
in the thymus) numbers. They found that high doses of genistein
(200 mg/kg/day) resulted in near total elimination of some sub-populations
of thymocytes, and concluded that the impact of genistein on thymus
weight was probably caused by the increase in thymocyte death. But
even relatively low genistein concentrations (2 mg/kg; 2 parts per
million) had significant impacts on thymic weights in young mice,
decreasing weight by 30%. The difference in impact between mature
(figure above) and immature is consistent with prior experimental
work demonstrating that immune function in immature animals is generally
more sensitive to experimental treatment.
et al. also determined that genistein treatment suppressed
immune system function. For example, genistein-treated animals produced
lower amounts of antibodies following immunization. Genistein's
effect was powerful: 8 mg/kg reduced antibody formation by more
than 50%, and additional genistein suppressed antigen levels
even further in a a dose dependent fashion.
effect of increasing amounts of genistein on antigen levels
in juvenile mice when challenged with an antigen to which
they had been previously immunized.
another series of experiments, Yellayi et al. determined
how the blood levels of genistein achieved in their experimental
treatments above, by injection, compared to genistein levels in
human infants fed soy. This was an important measurement because
it is possible that the digestive treatment of genistein in soy
formula would lead to lower levels than those used in these experiments.
found that genistein levels in mice injected with 8 mg/kg were comparable
to those that have been measured the blood of soy fed infants for
several hours after feeding. They conclude that "genistein
injected at an 8 mg/kg per day dose in mice produces peak blood
levels "comparable to those in soy-fed infants" and that
leevel induces immune system abnormalities.
explore this further, they asked whether feeding mice genistein
produced similar results to those caused by injections. They found
that thymus weights declined when mice were fed genistein-enriched
diets, and that the serum levels of genistein in the mice
caused by the addition of genistein to their diets was significantly
less than what is observed in the serum of human infants fed soy
formula. In other words, kids fed soy formula are exposed
to genistein in their blood at levels that cause significant immune
system impairment in mice.
does it mean? The bottom line is that the US should
move to restrict the use of soy protein in infant formula.
There is enough evidence now to support this precautionary step.
Britain has already made this decision, restricting soy formula
only to infants with no other choice (for example, because of lactose
intolerance). Steps should also be taken to identify other uses
of soy protein that may enter infant's diets, for example as additives
to baby food.
results indicate that the developing immune system can be derailed
by exposure to genistein at levels infants ingest from soy formula.
While much remains to be done scientifically to reach firm conclusions,
Yellali et al. give a series of examples from the literature,
studies comparing immune function at later stages in life of infants
fed soy-based formula vs. cow milk formula:
et al. found that women fed soy formula as
infants were much more likely to use allergy and asthma drugs
as adults, indicating their immune systems were functioning
et al. reported that gamma globulins and
immunoglobulins were decreased in soy-fed infants compared
to infants fed on cow milk formula, and also that T cell
function shows greater impairment in soy-fed infants.
et al. also showed that infants fed soy have
reducted levels of antibodies against a series of diseases
(polio, tetanus, diptheria and pertussis) compared with similarly
vaccinated children who had been fed cow milk formula.
another study, Zoppi et al. demonstrate that
upper respiratory infections and bronchitis increased in soy-fed
et al.'s study of genistein impacts on mouse immune system
function is important because it begins to get at the mechanisms
by which effects seen in humans might be caused, and because they
have shown these mechanisms operate at levels of genistein exposure
regularly experienced by infants feeding on soy-based formula.
evidence from the human and animal studies is available already,
however, to justify precautionary steps. The US Food and Drug Administration
should immediately reassess its recommendations, using a scientific
panel that is immune from pressure from the soy industry. With a
truly independent and objective review, the FDA would be in a better
position to make a sound judgement.