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Endocrine FunctionMen’s HealthProteinWomen’s Health

Isoflavone Fears in Article Unfounded

October 25, 2019

by Dr. Mark Messina

A recent article on the Impossible Burger in the Washington Post (WP) included statements about the possible harmful effects of isoflavones. Before addressing these inaccuracies, it is important to highlight that the isoflavone content of different soyfoods varies quite markedly depending upon how it is made.

A 4 oz. serving of the Impossible Burger contains <2 mg of isoflavones, according to the company that produces this product, Impossible Foods. To put that amount into perspective, a cup of soymilk made from whole soybeans contains about 25 mg isoflavones.1 Mean isoflavone intake among older native Japanese consumers ranges from 30 to 50 mg/day.1 Thus, even if the WP article cited legitimate concerns about isoflavones, they would not be relevant to the Impossible Burger, regardless of how many you ate.

Now, to the misinformation.

“Soy contains estrogen-like compounds called isoflavones that some findings say can promote the growth of some cancer cells, impair female fertility and mess with men’s hormones.”

This WP statement is actually true if you isolate “some findings,” but it is misleading to do so and sets a pretty low bar for accuracy. There are 1,000 soy-related peer-reviewed articles published yearly. If you set your threshold for accuracy to “some findings” you can say whatever you want about isoflavones (or any other dietary component), especially if you include in vitro and animal studies. That isn’t what scientists do when reaching conclusions about diet and public health. They focus on the totality of the evidence and emphasize findings from intervention studies and secondarily, prospective epidemiologic studies.

Men’s Hormones

A 2010 meta-analysis of the clinical data found that neither soyfoods nor isoflavone supplements significantly affect testosterone, sex hormone binding globulin, free testosterone or the free androgen index.2 This analysis included 15 placebo-controlled treatment groups with baseline and ending measures. In addition, 32 reports involving 36 treatment groups were assessed in simpler statistical models to ascertain the results.

Over the past decade quite a few more studies evaluating the impact of soy on testosterone have been published. An updated, soon to be published analysis, which includes 700 more study participants than the 2010 analysis, concurs with those initial findings. In addition, the updated analysis shows no effect of isoflavone exposure on estrogen levels in men, which concurs with a previously published narrative review.3

Cancer cell growth

It has been known for decades that in vitro at low concentrations, isoflavones promote the growth of estrogen-sensitive cancer cells.4 At higher concentrations, which probably aren’t physiologically relevant, isoflavones inhibit cancer cell growth.4 Some animal studies show similar results, although the data are conflicting.4,5 However, in vitro and animal studies are at the bottom of the hierarchy of evidence. Fortunately, we have lots of insight about the effects of isoflavone exposure on estrogen-sensitive tissues and markers of cancer risk in humans. For example, isoflavone intake via supplements or foods has been found to not adversely affect breast tissue density in postmenopausal women (the group proposed to be at risk from isoflavone exposure)6-8 or breast cell proliferation,9-14 even when exposure exceeds typical Japanese intake. Furthermore, prospective observational data show post-diagnosis soy intake is associated with reduced breast cancer recurrence and mortality.15 The position of the American Cancer Society,16 American Institute for Cancer Research,17 World Cancer Research Fund International18 and the Canadian Cancer Society,19 is that breast cancer patients can safely consume soyfoods.

Female fertility

Concern about female fertility might at first glance appear nonsensical given the large populations of soyfood-consuming countries. On the other hand, fertility problems arose in Australian sheep grazing on a type of clover rich in isoflavones20 and in the captive cheetah residing in North American zoos fed soy.21 However, the relevance of these observations to humans is very questionable because cats metabolize isoflavones differently than humans and the sheep were exposed to huge amounts of isoflavones.22

More relevant are studies examining the effect of soy consumption on the menstrual cycle. Soy increases menstrual cycle length by about 1 day, although the effect is small, it was enough for some to speculate about infertility.23 In premenopausal women, soy also decreases levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) by about 20%.23 However, not only is the clinical significance of this finding, if any, unclear, but the investigators responsible for these findings were unable to determine if the effect on FSH and LH was due to isoflavones exerting an estrogen-like or antiestrogenic effect. What is clear from this research,23 as well as from a 1-year trial,24 is that soy does not prevent ovulation.

Interestingly, among women attending a fertility clinic who underwent in vitro fertilization, soy consumption negated the adverse effect of bisphenol A (BPA). That is, among non-soy consumers, urinary BPA levels were inversely related to live birth rate whereas among soy consumers, there was no effect of BPA.25

Whether you choose to incorporate the Impossible Burger or any soyfood into your diet is a personal choice. Claims that isoflavones have detrimental health effects, as reported in the WP article, are exaggerated.

References

  1. Messina M, Nagata C, Wu AH. Estimated Asian adult soy protein and isoflavone intakes. Nutr Cancer. 2006;55(1):1-12.
  2. Hamilton-Reeves JM, Vazquez G, Duval SJ, et al. Clinical studies show no effects of soy protein or isoflavones on reproductive hormones in men: results of a meta-analysis. Fertil Steril. 2010;94(3):997-1007.
  3. Messina M. Soybean isoflavone exposure does not have feminizing effects on men: a critical examination of the clinical evidence. Fertil Steril. 2010;93(7):2095-104.
  4. Hsieh CY, Santell RC, Haslam SZ, et al. Estrogenic effects of genistein on the growth of estrogen receptor- positive human breast cancer (MCF-7) cells in vitro and in vivo. Cancer Res. 1998;58(17):3833-8.
  5. Onoda A, Ueno T, Uchiyama S, et al. Effects of S-equol and natural S-equol supplement (SE5-OH) on the growth of MCF-7 in vitro and as tumors implanted into ovariectomized athymic mice. Food Chem Toxicol. 2011;49(9):2279-84.
  6. Hooper L, Madhavan G, Tice JA, et al. Effects of isoflavones on breast density in pre- and post-menopausal women: a systematic review and meta-analysis of randomized controlled trials. Hum Reprod Update. 2010;16(6):745-60.
  7. Wu AH, Spicer D, Garcia A, et al. Double-blind randomized 12-month soy intervention had no effects on breast MRI fibroglandular tissue density or mammographic density. Cancer Prev Res (Phila). 2015;8(10):942-51.
  8. Labos G, Trakakis E, Pliatsika P, et al. Efficacy and safety of DT56a compared to hormone therapy in Greek post-menopausal women. J Endocrinol Invest. 2013;36(7):521-6.
  9. Hargreaves DF, Potten CS, Harding C, et al. Two-week dietary soy supplementation has an estrogenic effect on normal premenopausal breast. J Clin Endocrinol Metab. 1999;84(11):4017-24.
  10. Sartippour MR, Rao JY, Apple S, et al. A pilot clinical study of short-term isoflavone supplements in breast cancer patients. Nutr Cancer. 2004;49(1):59-65.
  11. Palomares MR, Hopper L, Goldstein L, et al. Effect of soy isoflavones on breast proliferation in postmenopausal breast cancer survivors. Breast Cancer Res Treatment. 2004;88 (Suppl 1)4002 (Abstract).
  12. Cheng G, Wilczek B, Warner M, et al. Isoflavone treatment for acute menopausal symptoms. Menopause. 2007;14(3 Pt 1):468-73.
  13. Khan SA, Chatterton RT, Michel N, et al. Soy isoflavone supplementation for breast cancer risk reduction: A randomized phase II trial. Cancer Prev Res (Phila). 2012;5(2):309-19.
  14. Shike M, Doane AS, Russo L, et al. The effects of soy supplementation on gene expression in breast cancer: a randomized placebo-controlled study. J Natl Cancer Inst. 2014;106(9).
  15. Chi X-X, Zhang T. The effects of soy isoflavone on bone density in north region of climacteric Chinese women. Journal of clinical biochemistry and nutrition. 2013;53(2):102–7.
  16. Rock CL, Doyle C, Demark-Wahnefried W, et al. Nutrition and physical activity guidelines for cancer survivors. CA Cancer J Clin. 2012;62(4):242-74.
  17. American Institute for Cancer Research. Soy is safe for breast cancer survivors. https://www.aicr.org/cancer-research-update/2012/november_21_2012/cru-soy-safe.html (accessed Feburary 5, 2013). 2012.
  18. World Cancer Research Fund International. Continuous Update Project Report: Diet, Nutrition, Physical Activity, and Breast Cancer Survivors. 2014. Available at: www.wcrf.org/sites/default/files/Breast-Cancer-Survivors-2014-Report.pdf. Accessed December 10, 2014. 2014.
  19. Eating well after breast cancer. (Accessed October 25, 2019, 2019, at https://www.cancer.ca/en/cancer-information/cancer-type/breast/supportive-care/eating-well-after-breast-cancer/?region=on.)
  20. Bennetts HW, Underwood EJ, Shier FL. A specific breeding problem of sheep on subterranean clover pastures in Western Australia. Aust J Agric Res. 1946;22131-8.
  21. Setchell KD, Gosselin SJ, Welsh MB, et al. Dietary estrogens–a probable cause of infertility and liver disease in captive cheetahs. Gastroenterology. 1987;93(2):225-33.
  22. Whitehouse-Tedd KM, Cave NJ, Ugarte CE, et al. Dietary isoflavone absorption, excretion, and metabolism in captive cheetahs (Acinonyx jubatus). J Zoo Wildl Med. 2011;42(4):658-70.
  23. Hooper L, Ryder JJ, Kurzer MS, et al. Effects of soy protein and isoflavones on circulating hormone concentrations in pre- and post-menopausal women: a systematic review and meta-analysis. Hum Reprod Update. 2009;15(4):423-40.
  24. Anderson JJ, Chen X, Boass A, et al. Soy isoflavones: no effects on bone mineral content and bone mineral density in healthy, menstruating young adult women after one year. J Am Coll Nutr. 2002;21(5):388-93.
  25. Chavarro JE, Minguez-Alarcon L, Chiu YH, et al. Soy intake modifies the relation between urinary bisphenol A concentrations and pregnancy outcomes among women undergoing assisted reproduction. J Clin Endocrinol Metab. 2016;101(3):1082-90.