February 23, 2024

The Right Chemistry: My vegetarian goulash sparked deep dive into soy

Studies comparing life-long diets of breast cancer patients find that soy consumption has a protective effect.

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My interest in endocrine disruptors was sparked in a most curious fashion.

Back in the 1980s, there was a little fruit and vegetable store around the corner from us that also had a deli counter staffed by a Czech immigrant who fancied himself as a chef. One day he cooked up a batch of goulash that I thought lacked flavour because he had not used the proper Hungarian paprika. That prompted me to make my own version for him with the right stuff. He liked it! Since I had made a large pot, he started to package the leftovers for sale. As he was doing that, a customer asked if my dish contained meat. Somewhat stunned by the question, I replied, “it’s goulash, of course it contains meat.” “Too bad,” she replied, “I don’t eat meat.”  

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Hmmm, I thought. Concerns about eating meat, along with the benefits of a plant-based diet, were just starting to make headlines at the time, so the prospect of a vegetarian version of my concoction plopped into my mind. But what sort of protein could I use to replace meat? My culinary background certainly did not include tofu, but this soy milk curd seemed like a viable candidate. After some experimentation, I did manage to come up with a reasonable facsimile and I passed the recipe on to the “chef.” To my surprise, customers sang its praises.

Then one day I happened to be in the store when a customer commented that she would have liked to try “Dr. Joe’s Vegetarian Goulash,” but because she had breast cancer, she couldn’t. It contained soy, she said, and that had a form of estrogen that she was not allowed since her breast cancer was “estrogen receptor positive.” And with that comment my dive into the deep waters of “endocrine disruptors” began. 

Breast cancer has long been recognized as a scourge given that tumours can be visible. As early as 1500 BC, the Egyptian medical text known as the Ebers Papyrus described breast cancer as an incurable disease. Hippocrates, who postulated that health depends on the balance of four humours, namely blood, phlegm, yellow bile and black bile, speculated that the cause was an excess of black bile since tumours sometimes turn black.

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Over the years, many other theories were advanced, including Bernardo Ramazzini’s thesis in the 18th century that nuns had a high incidence of breast cancer because of a lack of sexual activity. German physician Friedrich Hoffman had a different view and suggested that the disease was caused by an excess of such activities. The 18th century also introduced the first effective treatment, surgical removal of the tumour. Then with the advent of anesthetics in the 19th century, radical mastectomy, along with the removal of lymph nodes, became the standard therapy. 

A connection between breast cancer and hormones first surfaced in 1895 when Scottish surgeon George Beatson removed the ovaries from a patient with an ovarian cyst, a common procedure at the time. The patient also happened to have breast cancer and Beatson noted a shrinkage of her tumour. A clue about this association did not emerge until 1906 when ovarian extracts were shown to stimulate the sexual reproductive cycle, or “estrus,” in female mammals. The “active ingredient” in the extract was finally isolated in 1929 and named “estrogen,” deriving from the Greek “oistros” for “mad desire,” and “gennan” to “produce.” An explanation for why removal of the ovaries resulted in shrinkage breast tumours now became apparent: estrogen feeds the tumour. 

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The mechanism by which this happens was uncovered by organic chemist Elwood Jensen in 1958. Estradiol, the specific estrogen produced by the body, binds to proteins in cells he termed “estrogen receptors.” The receptor-estrogen combo then migrates into the cell’s nucleus where it interacts with DNA and causes changes in the expression of specific genes. The result is irregular cell multiplication, the hallmark of cancer.  

The discovery of estrogen receptors also suggested a treatment for breast cancer. If these receptors could be occupied by some substance other than estradiol, then binding with estradiol, and hence the irregular cell multiplication could be prevented. That approach worked. Drugs such as tamoxifen bind to estrogen receptors and have become the mainstay of treatment for “estrogen receptor positive” cancers. Another approach is the use of “aromatase inhibitors,” drugs that block the activity of aromatase, an enzyme the ovaries use to produce estrogen.  

Now we are ready to tackle the soy issue. In the 1930s, Japanese chemists isolated “isoflavones,” compounds found in soy beans that a decade later were shown by British biochemist Edward Charles Dodds to trigger the same reactions in animals as natural estrogen. This introduced the concept of “phytoestrogens,” plant-derived compounds with estrogenic activity and raised the obvious question of whether soy products could “feed” breast tumours.

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Now, after literally thousands of published studies about soy and isoflavones, we have an answer. Although isoflavones do enhance the proliferation of breast cancer cells “in vitro” and can promote estrogen-dependent mammary tumours in rats that have had their ovaries removed, numerous human epidemiological studies have shown that there is no need to be concerned about isoflavones aiding and abetting breast cancer. Indeed, they are likely to do the opposite.  

The initial studies to explore the link between soy and breast cancer were prompted by the observation that soy consumption is far greater in Asia than in North America and that the incidence of breast cancer is substantially higher in North America than in Asia. Furthermore, genetics do not seem to be involved since descendants of Asian immigrants to North America take on the local eating pattern and are no longer protected. Add to this case-control studies that compare life-long diets of breast cancer patients with controls and find that soy consumption, if anything, has a protective effect. The protection seems to be the greatest with significant soy consumption around the age of puberty. There are also prospective studies that have examined soy intake by patients after receiving a breast cancer diagnosis and found reduced mortality and reduced recurrence with increased consumption. 

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How then is it that isoflavones, compounds that definitely do bind to estrogen receptors, are not implicated in causing mischief? The answer appears to lie in the relative strengths with which the two substances bind. Isoflavones bind too weakly to activate the receptors, but by occupying the binding sites they prevent them from engaging with estradiol.  

Unfortunately, the commercial version of my vegetarian goulash disappeared when the store went out of business. If it were still available, I would have no hesitation in recommending it to anyone. I have no fear of phytoestrogens, chemicals that incidentally are also antioxidants and are found in many fruits and vegetables. To be honest, though, as far as taste goes, my tofu goulash does lack something. Meat.  

Joe Schwarcz ([email protected]) is director of McGill University’s Office for Science & Society (mcgill.ca/oss). He hosts The Dr. Joe Show on CJAD Radio 800 AM every Sunday from 3 to 4 p.m.

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