There is probably no more confusing area related to the health effects of soy than the relationship between soy intake and breast cancer risk. Soy is a rich and primary dietary source of the phytoestrogen class known as isoflavones. Isoflavones are present in relatively large amounts in virtually all soy foods. The primary isoflavones found in soy, genistein and daidzein, are structurally like human estrogen and can weakly mimic its effect in the body. But, phytoestrogens (isoflavones) genistein and daidzein, though structurally and functionally like 17 β-estradiol and estrone, are less bioactive. Concern over the possibility that the phytoestrogens in soy could stimulate breast tumor growth has led to much confusion among oncologists, health professionals and breast cancer patients.
Soybeans originated in Southeast Asia and were first domesticated by Chinese farmers around 1100 BC. By the first century AD, soybeans were grown in Japan and many other countries. Today the soybean is economically the most important bean in the world, providing vegetable protein for millions of people and ingredients for hundreds of chemical products. More than 2 billion people live in China, Japan, Korea and southeast Asia - and they consume on average more soy than the average American - every single day of their lives. However, the soy they consume is primarily fermented and fermented soy has been a part of their diet for thousands of years.
The soybean is one of the richest and cheapest sources of protein and is a staple in the diets of people and animals in numerous parts of the world. In East Asia the bean is extensively consumed in the forms of soy milk, a whitish liquid suspension, and tofu, a curd somewhat resembling cottage cheese. Soybeans are also sprouted for use as a salad ingredient or as a vegetable and may be eaten roasted as a snack food. Young soybeans, known as edamame, are commonly steamed or boiled and eaten directly from the pod. Soy sauce, a salty brown liquid, is produced from crushed soybeans and wheat that undergo yeast fermentation in salt water for six months to a year or more. Soy sauce is a ubiquitous ingredient in Asian cooking. Other fermented soy foods include tempeh, miso, and fermented bean paste.
Initially the low rate of breast cancer in these soy-consuming Asian countries led to the hypothesis that soy might reduce breast cancer risks. The initial support for soy’s preventive effect came from a 1990 study on rats, which found that 50% of soy-fed rats developed fewer mammary tumors.1 A second study in 1991 found that a soybean protein diet, low in methionine content, fed 5 weeks after carcinogen exposure significantly repressed mammary tumor progression.2 Since then, numerous subsequent research has shown that phytoestrogens in soy foods have been linked to lower incidences of breast and other cancers, improved heart health, and potentially lowered risk of osteoporosis.3, 4, 5, 6, 7, 8, 9, 10
What we know at this point is isoflavones have been shown to be estrogen blockers. In other words, they may block estrogen from reaching receptors and, therefore, potentially protect women from developing breast cancer. A 2006 study showed that dietary soy isoflavones antagonized estradiol (E2) effects on breast proliferation in a dose-dependent manner, altered estrogen receptor activity in the breast, and resulted in lower serum E2 concentrations. They concluded that a diet rich in soy isoflavones may have an estrogen-sparing effect in the postmenopausal breast, potentially limiting cancer risk associated with higher estrogen concentrations.11
Although Asians have consumed soy products for centuries, it is primarily used as a condiment and usually in fermented form, such as natto, miso, tempeh, gochujang, douchi, doenjang, and soy sauce. In Japan, Korea and China, the average person eats about an ounce of fermented soy each day, much less than the amounts of unfermented soy in American diets. Soy products promoted in the U. S. are generally unfermented, such as edamame, tofu, and soy milk, and as such have not undergone chemical changes that neutralize some potentially harmful compounds within soybeans. Few Americans regularly eat natto or its healthy fermented cousins - miso and tempeh.
Research has shown that soy proteins become more digestible with fermentation. The friendly bacteria or probiotics found in fermented soy help nourish the gut and digestive flora, boosting digestion and the absorption of nutrients. Because much of the immune system resides in the intestinal tract, these beneficial soy products also aid immune function. A significant percentage of soy proteins get broken down into shorter protein strands (called polypeptides) or even into single amino acids during the process of fermentation. These protein forms require less chemical activity in our digestive tract and are much better prepared for digestion than whole, intact proteins. Perhaps one of the most beneficial characteristics of fermented soy is the presence of vitamin K2. Vitamin K2 is an important vitamin, and it is not uncommon for people to be deficient in it.
Unfermented soy products like tofu and soy milk contain the following compounds that are disturbing to the body:
Lectins and saponins that are linked to altered bowel permeability, as well as other gastrointestinal and immune problems;
Oligosaccharides that abnormally affect the intestinal microbiome and cause gas;
Oxalates that are known to promote kidney stones;
Protease inhibitors that interfere with protein digestion and have caused malnutrition, poor growth; digestive distress and pancreatitis;
Phytates that block mineral absorption, causing calcium, zinc, and iron calcium deficiencies.
Cooking tofu does not reduce the level of phytates and other antinutrients. What does reduce these antinutrients is fermentation.
Soy is a widely planted genetically modified (GM) crop that is used to produce numerous genetically modified foods. Alarmingly, over 90% of the soy in the U.S. is genetically modified. There exists worldwide controversy over both health safety and environmental concerns of GM crops. That topic is too immense for through discussion here. In brief, as GM foods are increasinglyintroduced into our diet, concerns have been expressed regarding their safety. Animal toxicity studies with certain GM foods have shown that they may toxically affect several organs and systems. The results of several studies with GM foods indicate that they may cause some common toxic effects such as hepatic, pancreatic, renal, or reproductive effects and may alter hematological, biochemical, and immunologic parameters.12 Additionally, an overall reduction in phytoestrogen levels of 12-14% has been observed in the genetically altered soybean strains, mostly attributable to reductions in the concentrations of genistein and, to a lesser extent, in daidzin.13 This of course reduces the therapeutic effectiveness of the soy isoflavones. Research with animals and clinical trials are ongoing, but several countries have elected to err on the side of safety and restrict GM crops.
Overall, data reflects that the consumption of soy does not increase the risk of developing breast cancer, or that soy consumption in anyway adversely affects the survival of breast cancer patients. However, many feel that data on soy and breast cancer is still not conclusive, and more research is needed before any absolute dietary recommendations can be made. Furthermore, most studies that show any negative effects of soy either used pure genistein, which is a single component of soy rather than a more natural form of soy as a food. Soybean products are always eaten cooked or fermented. Some researchers conclude that only GM soy causes problems.
A case control study published in Lancet of women in Singapore, involving 200 case subjects and 420 control subjects, found that women with the highest consumption of soy-based products had a markedly decreased risk of developing breast cancer.14 Another study, a very large population-based, prospective study of 21,852 Japanese women aged 40-59, found that women with the highest intake of miso soup (a fermented soy) and soy isoflavones reduced their risk of breast cancer by up to 54%, compared with women with the lowest intake of soy isoflavones.15 A Chinese study, published in 2009 in the Journal of the American Medical Association, investigated the association between soy food intake and breast cancer survival among Chinese women diagnosed with breast cancer. The researchers found that higher soy intake was associated with increased survival and reduced recurrence of breast cancer. Their conclusion was “Among women with breast cancer, soy food consumption was significantly associated with decreased risk of death and recurrence.”16 Because diets in countries such as China, Japan and Malaysia are much higher in fruit and vegetable consumption than the U.S., this might also account for reduced cancer rates. That same year, 2009, the Life after Cancer Epidemiology study was published entitled Breast Cancer Research and Treatment and involved American women with breast cancer who consumed isoflavones at levels comparable to Asian populations. The researchers found that the women had reduced risk of breast cancer recurrence while on isoflavones, especially if they were also on tamoxifen therapy.17 A 2013 meta-analysis published in Asian Pacific Journal of Cancer Prevention concluded that soy food intake might be associated with better survival, especially for estrogen receptive (ER) negative, ER+/PR+, and postmenopausal patients.18
Lastly, a 2017 study examined the association between dietary intake of isoflavone and all‐cause mortality in 6,235 women diagnosed with a first primary breast cancer who had been followed for a median of >9 years. Overall, the researchers observed 21% lower all‐cause mortality associated with high isoflavone intake. The reduced mortality was largely confined to women who had ER‐negative/PR‐negative tumors and those who did not receive hormone therapy. They concluded high isoflavone intake may be associated with lower mortality only for women with ER‐negative/PR‐negative tumors or those who do not receive hormone therapy as part of their cancer treatment.19
Another issue is hexane, which is a byproduct of gasoline refining. Hexane is a neurotoxin and hazardous air pollutant. Soybean processors use it as a solvent and an inexpensive and efficient way of extracting oil from soybeans. Most soy protein ingredients in meat analogs and nutrition bars, which are listed on labels as soy protein isolate, soy protein concentrate or textured vegetable protein, have undergone hexane processing. Whole soybeans are literally bathed in hexane to separate the protein from the soybean oil. Hence, to avoid hexane-treated soy foods, look for “100% organic” products with the USDA seal, since hexane is banned in organic food production. A label that just says “made with organic” ingredients does not guarantee that all ingredients are hexane-free.
Considering the data, the idea that all soy foods should be completely avoided by women diagnosed with breast cancer is probably too drastic. However, soy supplements and heavily processed products, such as soy cheese, soy hot dogs, soy turkey and soy meat analogs, soy bars, soy yogurts, or soy protein powders, usually only contain soy protein isolates rather than nutrition from the whole soybean. These products should probably be avoided. As with all plant foods, the less they are processed, the better.
For clarity, soy products can be classified into two main groups: fermented and unfermented. Fermented is more traditional and generally safer and more nutritious than non-fermented. There are also another two sub-groups: organic and genetically modified (GM). GM soy should be avoided until conclusively proven safe. Many are of the opinion that the hazards of GM are some of the worst innovations of modern day bio-technology. Not only have GM products been shown to be potentially unhealthy to humans and animals, but also to the naturally-occurring plants that grow in the surrounding areas - since wind causes cross-pollination, resulting in mutated species of what were once natural variations of plants.
In summary, when buying soy, use only organic, non-genetically modified soy products, and preferably fermented or cultured with probiotics. Consume non-fermented soy products (such as tofu, edamame, soy protein, and soy oil) in strict moderation, if at all.
Notes
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1. Barnes, S., Grubbs, C., Setchell, K. D., & Carlson, J. (1990). Soybeans inhibit mammary tumors in models of breast cancer. Progress in clinical and biological research, 347, 239-253.
2. Hawrylewicz, E. J., Huang, H. H., & Blair, W. H. (1991). Dietary soybean isolate and methionine supplementation affect mammary tumor progression in rats. The Journal of nutrition, 121(10), 1693-1698.
3. Potter, S. M., Baum, J. A., Teng, H., Stillman, R. J., Shay, N. F., & Erdman Jr, J. W. (1998). Soy protein and isoflavones: their effects on blood lipids and bone density in postmenopausal women. The American journal of clinical nutrition, 68(6), 1375S-1379S.
4. Anthony, M. S., Clarkson, T. B., & Williams, J. K. (1998). Effects of soy isoflavones on atherosclerosis: potential mechanisms. The American journal of clinical nutrition, 68(6), 1390S-1393S.
5. Chen, Y. M., Ho, S. C., Lam, S. S., Ho, S. S., & Woo, J. L. (2003). Soy isoflavones have a favorable effect on bone loss in Chinese postmenopausal women with lower bone mass: a double-blind, randomized, controlled trial. The Journal of Clinical Endocrinology & Metabolism, 88(10), 4740-4747.
6. Sarkar, F. H., & Li, Y. (2003). Soy isoflavones and cancer prevention: Clinical science review. Cancer investigation, 21(5), 744-757.
7. Adlercreutz, H. (2002). Phytoestrogens and breast cancer. The Journal of steroid biochemistry and molecular biology, 83(1-5), 113-118.
8. Cassidy, A., Bingham, S., & Setchell, K. D. (1994). Biological effects of a diet of soy protein rich in isoflavones on the menstrual cycle of premenopausal women. The American journal of clinical nutrition, 60(3), 333-340.
9. Ingram D, Sanders K, Kolybaba M, Lopez D: Case-control study of phyto-oestrogens and breast cancer. Lancet 350: 990–994, 1997.
10. Pietinen P, Stumpf K, Mannisto S, Kataja V, Uusitupa M, Adlercreutz H: Serum enterolactone and the risk of breast cancer. A case control study in Eastern Finland. Cancer Epidemiol Biomarkers Prev 10: 339–344, 2001.
11. Wood, C. E., Register, T. C., Franke, A. A., Anthony, M. S., & Cline, J. M. (2006). Dietary soy isoflavones inhibit estrogen effects in the postmenopausal breast. Cancer research, 66(2), 1241-1249.
12. Dona, A., & Arvanitoyannis, I. S. (2009). Health risks of genetically modified foods. Critical reviews in food science and nutrition, 49(2), 164-175.
13. Lappé, M. A., BAILEY, E. B., CHILDRESS, C., & SETCHELL, K. D. (1998). Alterations in clinically important phytoestrogens in genetically modified, herbicide-tolerant soybeans. Journal of Medicinal Food, 1(4), 241-245.
14. Lee, H. P., Lee, J., Gourley, L., Duffy, S. W., Day, N. E., & Estève, J. (1991). Dietary effects on breast-cancer risk in Singapore. The Lancet, 337(8751), 1197-1200.
15. Yamamoto, S., Sobue, T., Kobayashi, M., Sasaki, S., & Tsugane, S. (2003). Soy, isoflavones, and breast cancer risk in Japan. Journal of the national cancer institute, 95(12), 906-913.
16. Shu, X. O., Zheng, Y., Cai, H., Gu, K., Chen, Z., Zheng, W., & Lu, W. (2009). Soy food intake and breast cancer survival. Jama, 302(22), 2437-2443.
17. Guha, N., Kwan, M. L., Quesenberry, C. P., Weltzien, E. K., Castillo, A. L., & Caan, B. J. (2009). Soy isoflavones and risk of cancer recurrence in a cohort of breast cancer survivors: the Life After Cancer Epidemiology study. Breast cancer research and treatment, 118(2), 395-405.
18. Chi, F., Wu, R., Zeng, Y. C., Xing, R., Liu, Y., & Xu, Z. G. (2013). Post-diagnosis soy food intake and breast cancer survival: a meta-analysis of cohort studies. Asian Pacific Journal of Cancer Prevention, 14(4), 2407-2412.
19. Zhang, F. F., Haslam, D. E., Terry, M. B., Knight, J. A., Andrulis, I. L., Daly, M. B., ... & John, E. M. (2017). Dietary isoflavone intake and all‐cause mortality in breast cancer survivors: The Breast Cancer Family Registry. Cancer, 123(11), 2070-2079.