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. SoyOnlineService.co.nz 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.”

FoodRenegade.com claims:

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

Finally WestonAPrice.org 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.

8 comments:

  1. good research and good read. thanks.

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  2. I love what your doing here. I'm not sure why I didn't find your blog when doing research for my own over at http://skepticalvegan.wordpress.com

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  3. Thank you very much for your work here!! I still get sent links to the Weston Price publications on this topic by concerned family members - this really helps. I appreciate the high quality of your work. Thanks for turning your "skeptical eye" to this topic (love that nod to skeptoid.com!)

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  4. Awesome article. Simply awesome. Thank you!

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  5. This really hasn't been studied well. Infant formulas are mainly produced by pharmaceutical companies. (Pharmaceutical giants Bristol-Myers Squibb (Enfamil)& Abbott Laboratories (Similac)) Large pharmaceutical companies are major providers of research funding and this leaves me with concerns of bias. And I'm not alone with these concerns:

    "It has been brought to light by several studies reviewing the medical literature that a significant proportion of safety and efficacy data generated and published in industry-sponsored clinical trials is biased in favor of that company’s product."
    http://www.americanbar.org/newsletter/publications/aba_health_esource_home/Morrissey.html

    Everything I've read says there needs to be more research. I don't see those big Pharm companies leading the way to show that these isoflavones are potentially harmful.

    "Urinary concentrations of genistein and daidzein were about 500 times higher in the soy formula-fed infants than in the cow milk formula-fed infants... whether phytoestrogens in soy formula are biologically active in infants is still an open question."

    http://www.nature.com/jes/journal/v19/n2/abs/jes200844a.html

    As long as there are still questions about these products, I see no reason to feed them to infants or children. And personally, because of the goitrogenic effects, I as an adult with a history of hypothyroidism, will be avoiding soy in general. http://www.thyroid.org/patients/ct/volume4/issue6/ct_patients_v46_12_13.html

    Elizabeth McWhirter, R.N. (prn@scavengersr.us)

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  6. Respectfully, it's your calculation of 1/10th to 1/25th a Pill's worth of estrogen (remembering that the Pill functions by quite flooding a woman's body with estrogen -- although admittedly the phytoestrogens have a much more

    complicated mode of action, and at some doses their estrogen-binding effects may be more pronounced than their estrogen-mimicking effects, which as you note are relatively weak) that's incredibly misleading - could you please show us

    the math? I'm still clueless as to how you got it because the calculation you show, with "generous" assumptions that make it fairly useless, would predict 1000 Pills per serving, and no one claims that. (The number thrown around is

    5, the numbers on which I haven't verified either).

    Re: the University of Iowa study, I'd respectfully submit that you only read the abstract and conclusions; apart from the fact that the study was very poorly designed (just calling people on the phone and asking HIGHLY SUBJECTIVE

    questions re: health instead of tracking them down and taking any kind of physical measurements, and the study contained no data on how long each person recieved the formula/how much each received - which is essential since toxicology

    isn't just a binary science), the abstract and conclusion "neglect" to mention some crucial facts found in the body of the paper: the researchers "adjusted" for the presence of polycystic ovarian syndrome, blocked fallopian tubes,

    pelvic inflammatory disease, hormonal disorders and multiple births, treating them as confounding variables - when we need to find out whether these are caused by soy in the first place and can't dismiss them as potential confounding

    variables!!! Researchers didn't even ask about men's health as regards testosterone levels, genital size, incidence of homosexuality or gender identity issues, etc., let alone actually take measurements. Of note, a "generous grant"

    from the Infant Formula Council sponsored the study! Plus, the Fomon Infant Nutrition Unit at the University of Iowa is heavily funded by the Formula industry. The full text is available on the web for free. If you're interested

    I'll share some studies showing soy's dangers, not sure if this will get read or not so I won't go to the trouble if not.

    Anyways, it didn't even acknowledge soy's other potential problems - eg. the goitrogenicity of some antinutrients (including isoflavones) - as no mention of thyroid health is to be found in the paper.

    Ultimately, if phytoestrogens aren't harmful to us, then why the hell are they in the plant? Does it want to be eaten? Or does Dog really love us so much that he designed plants to selflessly enhance human health???

    If you advocate veganism primarily for ethical reasons, how likely is it that those ethics exactly coincide with optimal health? Why not acknowledge some potential vegan health problems due to plant toxicities - then you can discuss

    how to optimize health on a vegan diet, without denial that would either inhibit your own research or turn people off from the ethical considerations of veganism. I really think we should be able to agree that babies in particular

    should be exclusively fed breast milk, not formula based on cow's milk (with its deformed casein if A1 among many other problems) and certainly not formula based on something loaded with goitrogens, phytoestrogens, phytic acid, very

    high levels of manganese, protease inhibitors, etc.

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  7. "Outbred female CD-1 mice were treated on days 1–5 with equivalent estrogenic doses of DES (0.001 mg/kg/day) or genistein (50 mg/kg/day). At 18 months, the incidence of uterine adenocarcinoma was 35% for genistein and 31% for DES" Sure, toxicity varies a lot from species to species and infants aren't getting 50mg/kg/day of genistein thankfully, but that's far from convincing that Dog made soy plants for our exclusive benefit.

    From _Uterine Adenocarcinoma in Mice Treated Neonatally with Genistein_ Cancer Research June 1, 2001.

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