Our Stolen Futurea book by Theo Colborn, Dianne Dumanoski, and John Peterson Myers
 
 

 

 

Yellayi, S, A Naaz, MA Szewczykowski, T Sato, JA Woods, J Chang, M Segre, CD Allred, WG Helferich and PS Cooke. 2002. The phytoestrogen genistein induces thymic and immune changes: A human health concern? Proceedings of the National Academy of Sciences 99:7616-7621.


press coverage of research

 
 

 

Yellayi 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.

Britain 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.

What 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 formula.

What 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 thymus weight.

Genistein 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 receptor.

from Yellai et al. 2002

 

Genistein 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.

Yellayi 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.

 

The effect of increasing amounts of genistein on antigen levels in juvenile mice when challenged with an antigen to which they had been previously immunized.

In 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.

They 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.

To 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.

What 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.

These 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:

  • Strom 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 differently.
  • Zoppi 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.
  • Zoppi 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.
  • In another study, Zoppi et al. demonstrate that upper respiratory infections and bronchitis increased in soy-fed formula infants.

Yellali 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.

Enough 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.

 

 

 
     

 

 

 

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