Monday, March 17, 2008

Dr. Jill Schneider - Lehigh University (imported article)

Answers to FAQs about Soy Isoflavones, Soy Infant Formula and Puberty

This is not my main field of research and expertise. The reason I am writing this is that I supervised a research project on the effects of genistein, a soy isoflavone, on puberty in hamsters (view a PDF of the power point presentation ). We presented this work at the Society for Neurosciences meeting in 2001. It received a great deal of press (far beyond the merits of the work), and I still receive emails every week from parents who want to know whether their child's precocious puberty might be due to having been fed soy infant formula. I don't know the answer to this question. I'm sorry to be of so little help. I hope something on this page might point you in the right direction.

Q: What are isoflavones?

A: Isoflavones are a class of chemical compounds. Genistein and daidzein are two isoflavones found in soy beans. These and other isoflavones are actually in many different kinds of legumes (beans), grains and vegetables.

The structure of the isoflavone molecule shares some critical similarities to estrogen, one of the hormones naturally produced in our own bodies (both male and female). Estrogen is, of course, produced in female ovaries and male testes, as well as in fat cells and certain brain cells. We also have special cells in our brains, reproductive organs , liver and fat cells that respond to estrogen, by virtue of the estrogen receptors in these cells.

Isoflavones can bind to these estrogen receptors.

The structure of isoflavones is not exactly the same as estrogen, so isoflavones are not estrogen. However, the isoflavone structure has important similarities to estrogen. These similarities allow isoflavones to bind to estrogen receptors in our estrogen-responsive cells. Don't take my word for it. Feast your eyes on the structure of these two molecules to see how they are similar (estrogen left, genisteiin right).

molecules

Because isoflavones come from plants, and because they are similar to estrogen, isoflavones are placed by scientists into a larger category known as phytoestrogens.

(Phyto = plant )

Q: What do soy isoflavones and other phytoestrogens have to do with puberty?

A: Puberty is the maturation of the reproductive system, and one important event in the final maturation of the reproductive system is the increase in synthesis and secretion of estrogens (a natural type of steroid hormone).

Puberty involves more estrogen binding to estrogen receptors, and isoflavones also bind to estrogen receptors.

Estrogens act on the brain areas that control maturation, menstrual cycles and fertility. They also act on the breasts, uterus, bones, fat cells, and parts of the brain involved in memory and other behaviors. Most of estrogen action is thought to happen when estrogen enters cells and binds to special estrogen receptors that lie inside the cells. The estrogen has a special binding site that allows it to recognize and bind to the estrogen receptor, like the way that a key (estrogen) fits its own special lock (estrogen receptor). The estrogen binds to estrogen receptors and form an estrogen-receptor complex (other molecules join in this complex). This estrogen receptor complex moves into the cell nucleus, starts a cascade of chemical reactions, which culminates in the estrogen-receptor (ER) complex sitting down on the DNA (yes, the genetic material). The effect of the ER complex sitting down on the DNA is to start turning genes on or off (this is called gene expression). Turning on a gene leads to the formation of a new protein (such proteins might be enzymes, hormones, or factors that turn on other genes). These changes in gene expression result in new proteins involved in puberty, fertility, bone growth, learning, etc. See my references at the end if you want to know more about estrogen action. (By the way, when the ER complex sits down on the DNA of some types of cancer cells, it promotes growth and cell division of those cancer cells.)

Q: If soy isoflavones bind to estrogen receptors, is this good or bad?

We don't have enough information to answer this. We do have enough information to say that the answer will not be a simple "yes" or "no."

In some cases, when isoflavones bind to the estrogen receptor, the effect is similar to the effect of estrogen. In other cases, isoflavones bind to the estrogen receptor and block the effects of estrogen.

Sometimes isoflavones mimic estrogen

Sometimes isoflavones block estrogen binding to its receptor

We know, for example, that treatment of female baby rats with estrogen will advance the onset of puberty, that is, puberty will occur earlier in the estrogen-treated rats. If soy isoflavones act like estrogen, we would expect rats fed isoflavones to reach puberty earlier than those that did not receive isoflavones. On the other hand, if soy isoflavones block the effects of estrogen when they bind to the estrogen receptor, we would expect puberty to be delayed in female rats given soy isoflavones.

Since estrogen rises at puberty, and puberty also involves changes in the body's ability to respond to estrogen, and many babies are raised on soy infant formula containing isoflavones, and the age of puberty has been decreasing over the past 30 years, it is reasonable to wonder whether the isoflavones in soy infant formula affect puberty. Do soy isoflavones advance or delay the onset of puberty? To perform this experiment on human babies is out of the question. This is why my student, Jamie Swanson and I fed baby hamsters the soy isoflavone genistein and monitored signs of pubertal development.

The results of our study on hamsters were very clear. Feeding the soy isoflavone, genistein advanced the onset of puberty. At the first ovulation we stopped the isoflavone treatment and two weeks later, we tested the females for sex behavior with a sexually-experienced adult male hamster. Those that had been fed the isoflavones were quicker to show sex behaviors characteristic of the adult female, suggesting that early isoflavone treatment has long lasting effects on the nervous system that affect behavioral motivation and performance.

Again, You can open a PDF of the whole study here.

Q: If you found that genistein advanced the onset of puberty in hamsters, does this mean that soy infant formula causes early onset of puberty in girls?

No. It simply suggests that more research should be done before giving soy infant formula to babies.

Please keep the following points in mind:

  1. This study was done in hamsters, and there is no guarantee that the effects of genistein in this study can be generalized to human beings.
  2. This study used only one isoflavone and cannot necessarily be used to generalize to other isoflavones (such as daidzein)
  3. This study gave a large dose of one isoflavone and cannot be used to generalize to soy infant formula or other soy products, which contains a variety of isoflavones at different doses. Some of those isoflavones mimic estrogen's effects, some of them block estrogen's effects, and the effects differ from tissue to tissue and species to species.
  4. The take home message from the hamster study is: Compounds in soy products have effects on the reproductive system in mammals, including long lasting effects on behavior, probably by binding to estrogen receptors.

You must draw your own conclusions from my study, but my conclusion is this:

More research should be done on soy isoflavones before feeding soy infant formulas to babies.

Q: Is there other research being done on soy infant formula?

Yes. Since my study was presented in 2001, many studies have been done on other rodents, nonhuman primates, and at least one small study was done on humans. The monkey and rodent studies have confirmed what our hamster study found, and the study on humans found no significant effect of soy infant formula on children's health including puberty. There are other studies in progress that will examine the long-term effects. Because the researchers want to know the long-term effects, the studies will take many years to complete. All of the references appear at the end of this FAQ sheet.

Q: Soy isoflavones come from natural organically grown nonmeat vegan-approved sources; how could they be harmful?

Lots of natural things are harmful (apple seeds, poison ivy, belladonna (deadly nightshade)). More important, soy milk and soy infant formula are about as natural as Coca Cola. The soy beans and the bean plants are "natural," but the products are unnatural. To make soy milk and formula, the beans are processed chemically to extract and concentrate the protein and fat components, which are then mixed with lots of sugar (quite often it's high fructose corn syrup, a whole other story). Soy milk and infant formula are more calorically dense than any "natural" food, including breast milk. When our pre-agricultural ancestors ate various beans and plants, they probably never experienced soy isoflavones at the high concentration of soy milk, nor did they consume liquid drinks with the high caloric value of soy milk. Soy milk, soy infant formula, tofu, tempeh, etc. are not natural, they are highly processed food products made from a natural bean.

Some people equate soy products with various "good" things such as fresh, unprocessed, organically grown vegetables, the healthy "Asian diet," and so forth. These people are under the erroneous impression that the makers and purveyors of soy products are in a different moral, ecological category than those in the meat and dairy industry. To the contrary, the soy industry is a huge agribusiness. Most soy is sold by Archer Daniels Midland, a Fortune 500 company quite well known for receiving enormous subsidies ("corporate welfare") and price fixing (see the Wikipedia entry for starters ). The soy lobby is one of the most powerful political lobbies, right on par with the meat and dairy lobbies.

The fact that soy beans are marketed by giant corporations doesn't make the beans good or bad, healthy or unhealthy. The point is, the vast majority of these soy products are not being sold and marketed by well-meaning, small, family farmers and gardeners with a commitment to your health. They are simply another kind of processed food with possible health benefits and possible side effects. Got soy?

Q: How can I make sense of all this?

You have to keep in mind the source of the information. All the information in the popular press is biased, both pro-soy and anti-soy. There are very dramatic anti-soy websites and publications, and these can be traced, usually, to meat and dairy industry/lobby types { here is one example of a rabid attack on soy }. The vast majority of what you see in the popular press is the positive spin on soy promoted by the soy lobby/industry and all the natural food industry people who benefit from selling soy products and selling you their own version of a "healthy" life stye. In addition, there is a pro-soy component of feminists who have fallen prey to the pro-soy lobby { here is an example of this uninformed point of view }

Sigh.

Here is what I think might be an objective website on soy (knock on wood).

For objective, primary scientific literature that is relatively free from the influence of corporations, you can search on your own for journal articles published by university scientists on PubMed or Google Scholar. These are not without bias, but at least the editors of these journals require all authors to make full disclosure of all financial interests. You can easily determine who sponsored the research (whether it was Archer Daniels Midland, the U.S. Food and Drug Administration or the National Institutes of Health) so you can see through to the motivations that underlie the research.

On a related topic, it is important to know that one reason our government gives research grants to university scientists is so that we can do controlled experiments to try and answer these questions without having industry influence the outcome of the experiments and without having industry influence our ability to disseminate the results. As corporations become more and more involved in government-funded research projects, this essential objectivity will diminish rapidly.

Q: My daughter reached puberty very early and I raised her on soy infant formula; should I feel guilty?

No. But, I'm a mom too, and one of my children has had a multitude of medical issues, so I certainly empathize with your feelings.

A few more useful points: The one small study that has been done on human infants found no significant effect of soy infant formula on children's health including puberty. In addition, there are many, many environmental factors that might cause precocious puberty in any particular child. It is impossible for any one individual to know which one was the culprit. There are many different molecules that bind to estrogen receptors or turn into molecules that bind to estrogen receptors, and any one of these might influence the developing reproductive system (see this link):

  • Pesticides (chlordane, toxaphene, etc.)
  • Plastics (such as bisphenol and pthalates which leach out of plastic into food)
  • Effluent from industrial waste (nonyl phenol, dioxin, PCBs)
  • Hormones given to farm animals that we eat (dexamethasone)
  • Real estrogen and progesterone that are ingested as birth control pills and then excreted into the toilet, which then end up in our drinking water (water treatment systems clean up bacteria and other contaminants, but not steroids such as estrogen)

Feeling better? I know, it's depressing. We live in a " sea of estrogens " that are contributing to the increase in precocious puberty, hypospadia, ambiguous sexuality, infertility, cancer and who knows what else. At the same time, soy isoflavones are being sold to us as though they will protect against symptoms of menopause, osteoporosis, heart disease breast cancer, etc. The best you can do is keep learning. I will try to keep this site updated for you.

Thanks for your emails, and I'm sorry I cannot answer each one individually.

REFERENCES

Casanova, M., You, L., Gaido, K. W., Archibeque-Engle, S., Janszen, D. B., and Heck, H. A. (1999). Developmental effects of dietary phytoestrogens in Sprague-Dawley rats and interactions of genistein and daidzein with rat estrogen receptors alpha and beta in vitro. Toxicol Sci 51(2), 236-44.

Giampietro, P. G., Bruno, G., Furcolo, G., Casati, A., Brunetti, E., Spadoni, G. L., and Galli, E. (2004). Soy protein formulas in children: no hormonal effects in long-term feeding. J Pediatr Endocrinol Metab 17(2), 191-6.

Levy, J. R., Faber, K. A., Ayyash, L., and Hughes, C. L., Jr. (1995). The effect of prenatal exposure to the phytoestrogen genistein on sexual differentiation in rats. Proc Soc Exp Biol Med 208(1), 60-6.

Piacsek, B. E., and Streur, W. J. (1975). Effect of exposure to continuous light on estrogen-induced precocious sexual maturation in female rats. Neuroendocrinology 18(1), 86-91.

Tan, K. A., Walker , M., Morris, K., Greig, I. , Mason, J. I., and Sharpe, R. M. (2006). Infant feeding with soy formula milk: effects on puberty progression, reproductive function and testicular cell numbers in marmoset monkeys in adulthood. Hum Reprod 21(4), 896-904.

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