Monday, November 2, 2009

Dangers of Phytoestrogens

Today we are going to turn our skeptical eye on the proclaimed dangers of phytoestrogens. What are phytoestrogens? Phytoestrogens are compounds, which due to their similarity to the estrogen estradiol used in our own bodies, are able to cause mild estrogenic or antiestrogenic effects. Phytoestrogens appear in many foods including soy, flax, sesame seeds, wheat, rice, apples, carrots, and many other foods. Opponents claim that because of the high concentration of these compounds in soy, eating soy foods at the levels present in our society is highly dangerous and causing a multitude of undesirable effects. claims:

“Phytoestrogens that disrupt endocrine function and are potent antithyroid agents are present in vast quantities in soy, including the potentially devastating isoflavone Genistein. Infants exclusively fed soy-based formula have 13,000 to 22,000 times more estrogen compounds in their blood than babies fed milk-based formula, the estrogenic equivalent of at least five birth control pills per day.” claims:

“An infant taking the recommended amount of soy formula is consuming a hormone load equivalent of 4 birth control pills a day!”

Finally claims:

“A recent study found that babies fed soy-based formula had 13,000 to 22,0000 times more isoflavones in their blood than babies fed milk-based formula.”

Which, if any, of these differing claims is true? While none of these websites cite sources, I was able to track down the original source of this claim published in The Lancet journal in 1997:

“Circulating concentrations of isoflavones in the seven infants fed soy-based formula were 13000-22000 times higher than plasma oestradiol concentrations in early life, and may be sufficient to exert biological effects, whereas the contribution of isoflavones from breast-milk and cow-milk is negligible.” Link

Note that this is not 13,000-22,000 times more isoflavones than non-milk fed infants or 13,000-22,000 times more estrogen compounds. This is stating that circulating isoflavone concentrations are 13,000-22,000 times higher than plasma oestradiol concentrations. Without some way to compare isoflavone concentrations to plasma oestradiol concentrations this is as meaningful as stating that saturated fat intake is thousands of times higher than vitamin B12 intake. How do isoflavones compare to estradiol?

Comparisons between isoflavones and estrogens are extremely complex. All isoflavones bond to human estrogen receptors extremely weakly. Of isoflavones, genistein binds most strongly, but it is still very weak relative to most estrogens. All isoflavones bond better to beta type estrogen receptors than alpha type receptors. For beta type receptors genistein binds almost as strongly as estradiol; although estradiol is about 10,000 times more potent at inducing transcription from this receptor.

“Even if genistein bound as efficiently as 17 beta -estradiol, the structural transformation of hER[human estrogen receptor] beta induced by genistein would not be sufficient to facilitate the binding of a coactivator. The induction of transcription by ERs[estrogen receptors] requires a coactivator.”

This study can be found here
Infants using soy formula generally take in about 4mg/kg/day in isoflavones. This includes both genistein and weaker isoflavones like daidzein. For an infant weighing 5kg, this would mean 20mg of isoflavones are taken in every day. How does this compare to birth control pills? Birth control uses both estrogen and progesterone to achieve its effects. Comparing to only estrogen is leaving out an important ingredient in the pill; however, pills vary from about 20mcg (.02mg) to about 50mcg (.05mg) of estrogen in the pills. Even if we assume that all of the isoflavones ingested by infants are the more strongly acting genistein, that genistein binds to beta receptors as strongly as estradiol, and that alpha receptors can be ignored entirely, the isoflavones ingested would still only be 1/10th to 1/25th of the equivalent of just the estrogen in a birth control pill, and all of these estimates are overly generous.

While the claims made by these anti-soy websites are either incredibly misleading or downright false, this says nothing about the actual safety of phytoestrogens. What impacts have phytoestrogens been found to have on human bodies?
From 1965 to 1975 the University of Iowa ran a controlled feeding study in which 248 infants were fed soy formula and 563 were fed dairy formula. Between March and August 1999 the now adults who had participated in this study were tracked down and asked to report on time of pubertal maturation, menstrual and reproductive history, height and usual weight, and current health.

“No statistically significant differences were observed between groups in either women or men for more than 30 outcomes. However, women who had been fed soy formula reported slightly longer duration of menstrual bleeding (adjusted mean difference, 0.37 days; 95% confidence interval [CI], 0.06-0.68), with no difference in severity of menstrual flow.”

The study concluded,

“Exposure to soy formula does not appear to lead to different general health or reproductive outcomes than exposure to cow milk formula. Although the few positive findings should be explored in future studies, our findings are reassuring about the safety of infant soy formula.”

This study was published in the Journal of the American Medical Association in 2001 and can be found here
A review of the literature on soy based infant formulas was published in the Journal of Nutrition in 2004 and concluded,

“SBIF[Soy-based infant formula] is well recognized as a healthy alternative to human or cow’s milk. It has a long history of safe use and is a high-quality, plant-based protein alternative for infant formula. Recent in-depth reviews of the safety of dietary isoflavones in soy have found that there is no conclusive evidence from animal or human adult or infant populations that indicates that dietary isoflavones may adversely affect human health development or reproduction. Comprehensive literature reviews and clinical studies of infants fed SBIFs have resolved questions or raise no clinical concerns with respect to nutritional adequacy, sexual development, neurobehavioral development, immune development, or thyroid disease. SBIFs provide complete nutrition that adequately supports normal infant growth and development.”

The entirety of this article can be found here
Currently, the Arkansas Children's Nutrition Center is conducting a longitudinal study comparing growth, development, and health of breastfed children with soy formula-fed and dairy formula-fed children from birth through age 6 y. “After 5 y of study, children in all 3 groups (n > 300) are growing and developing within normal limits, and there are no indications of adverse effects in the soy-fed children.” This study, published in the American Journal of Clinical Nutrition, can be found here
Most of the research on isoflavone use later in life has to do with breast cancer risk in postmenopausal women. Most research tends to conclude there is a reduced risk since the isoflavone genistein is antiangiogenic (blocks the formation of new arteries); although, for certain types of estrogen dependent breast cancers, slightly higher risks have been associated with higher isoflavone intake. Other cancers such as prostate and cervical cancer are less frequent with higher isoflavone intake, likely due to the antiangiogenic effects of the isoflavones. Isoflavones also tend to act as antioxidants, preventing free-radicals from causing damage to cells.

While a great deal of research can still be done to work out the details, soy and other phytoestrogen containing foods have and continue to be used in differing quantities throughout the world, and no evidence exists to suggest these phytoestrogens pose significant health risks to healthy adult or developing humans. Next time you hear clearly misquoted claims proclaiming the severe health risks of a common food on a poorly sourced website, remember to be skeptical!

Check out the new post on the dangers of phytates.