Soy and Estrogen Link: Real or Fake?
Some popular fitness and health-related sources tend to claim that the link between soy and estrogen is real. On top of that, they say that this connection has a harmful effect on men’s health. Let’s see where the truth is!
Soy and Estrogen Connection
Soybeans and products based on it can hardly be called popular types of food among men. However, protein soy isolates are included in sports nutrition, and soy concentrates are common in the food industry as fillers for various meat and sausage products, as well as meat surrogates.
Vegetarians are also active consumers of soy. They use it as a source of protein. The protein quality of soybeans is one of the most attractive reasons for the interest in soy and soy foods among vegetarians .
Recently, soy and high-protein products derived from it have been criticized for allegedly having unpleasant properties to influence men’s health, which is due to the content of phytoestrogens, isoflavones with a molecular structure similar to endogenous estrogens.
Knowing how many traditional food products are subjected to completely unreasonable demonization, I would like to understand the objectivity of the claims made to soy and estrogen.
Are Soy Isoflavones to Blame?
Isoflavones belong to the functional class of non-steroidal phytochemicals called phytoestrogens (which also include lignans and coumestans), which have a chemical structure and functions similar to endogenous estrogens in animals [2, 3].
The main isoflavones found in soybeans are genistein, daidzein, and glycitein. The isoflavone content of soy products varies between brands and products.
For example, in Canada, the isoflavones in soybeans range from 360 to 2241 mg/kg.
Isoflavones in soybeans from Romania are ranged from 210 to 1340 mg/kg, 1176-3309 mg/kg in the US, and 525-986 mg/kg in India.
Soy temperature and moisture are critical for the differential synthesis of soy isoflavones during plant growth, with the highest concentrations of isoflavones occurring at low temperatures and high soil moisture, mainly depending on the first one.
Interaction of Isoflavones With Estrogen Receptors
Isoflavones have the ability to interact with estrogen receptors (ER) due to their structural similarity to 17β-estradiol.
However, isoflavones have low estrogenic activity compared to estradiol .
Indeed, the affinity of soy isoflavones for ERa and ERß was found to be 1/1000 and 1/3 times, respectively .
Interacting with ERa, isoflavones exhibit an estrogenic effect, and with ERß, an antiestrogenic one. Genistein has a higher affinity for estrogen receptors than daidzein [5, 6, 7].
It has been suggested that soy isoflavones may act as selective regulators of tissue estrogenic activity and as a selective modulator of estrogen receptors, having mechanisms other than direct interaction with the receptor [8, 9, 10, 11].
Phytoestrogens produce estrogenic, antiestrogenic, or no activity depending on tissue [12, 13]. T
he estradiol receptors ERa and ERβ demonstrate different, often directly opposite effects in men and women; therefore, phytoestrogens do not show their activity as classical estrogen agonists .
Concerns about the adverse effects of soy consumption were originally based on animal data. Nowadays, it is well known about the difficulties of extrapolating the data of such studies to humans in everyday use .
In mouse models, for example, intrauterine exposure to estradiol was incomparable with that of a human due to a more than a millionth difference in concentration .
Monkeys, just like rodents, have a completely different metabolism of isoflavones [17-23].
Initially, a link between soy and estrogen/male fertility was postulated in 1940 after the recognition of endocrine disruption in sheep caused by red clover isoflavones, leading to a syndrome of infertility called “clover disease” .
It is also worth adding that the usual levels of consumption of soy products in various countries, including in Asia, even among people who adhere to vegetarianism, often do not lead to the intake of isoflavones in the body in quantities that could cause problems.
Unfortunately, this also reduces the beneficial effects of isoflavones. To obtain the beneficial effects of soy isoflavones, their intake must be at least 60-100 mg per day , which is currently difficult to achieve in Western countries.
The highest consumption of isoflavones is observed in the countries of East and South Asia (20-50 mg/day). In the USA, it is 0.15-3 mg, and in European countries, it is 0.49-1 mg [35, 36].
In general, the low content of bioactives in modern second-generation soy products and moderate amounts in traditional ones provide moderate health benefits with very limited risk of potential adverse health effects .
Effect of Soy Phytoestrogens on Sex Hormones
In humans, the disturbance of the sex hormone system and the problems of infertility associated with soy foods are in stark contrast to those seen in large populations of soy-consuming countries.
For example, reproductive health disorders, including feminizing effects, erectile dysfunction, and decreased libido, associated with a very high intake of isoflavones, have been reported.
Although the available data have found only minor harmful effects or no health effects at all [25, 26].
In clinical studies with high exposure to isoflavones in men, no estrogen-related disorders have been reported .
Conversely, sperm count, and motility were positively associated with isoflavone intake  or no correlation between isoflavone intake and sex hormones or sperm quality .
Testosterone levels were assessed in a meta-analysis of 32 clinical reports without a convincing interaction between consumption of soy or soy isoflavones and free testosterone concentration .
Most of the information about the interaction of soy with sex hormones has come from in vitro and in vivo studies , but not human studies.
In a recent paper on the hormonal effects of soy products, the authors concluded: “Clinical data show that neither soy foods nor soy protein, nor isoflavones affect circulating reproductive hormone levels in men or women.
However, some studies show that soy protein, but not isoflavones, affects insulin-like growth factor I (IGF-1). ” 
Regarding the effect on IGF-1, it should be clarified that it manifests itself in a small increase in circulating hormone in response to consumption servings containing more than 25 g of soy protein.
Similar effects are observed after consuming other types of protein. That is, in this regard, soy protein is just as good as others.
Conclusions on the Effects of Soy and Estrogen on Men’s Health
- Currently, there is no evidence of the negative effects of soy-based products on men’s health, and the available evidence (soy and estrogen link) comes from animal studies that are not applicable to humans;
- In those who regularly consume soy products, the typical intake of isoflavones, which are phytoestrogens, is low and often insufficient even to produce positive health effects, let alone the perceived risk of negative effects.
- Kumar P., Chatli M.K., Mehta N., Singh P., Malav O.P., Verma A.K. Meat analogues: Health promising sustainable meat substitutes. Crit. Rev. Food Sci. Nutr. 2017;57:923–932.
- Phytoestrogens: the biochemistry, physiology, and implications for human health of soy isoflavones. Setchell KD Am J Clin Nutr. 1998 Dec; 68(6 Suppl):1333S-1346S.
- Phytoestrogens. Cabot W. J Am Acad Orthop Surg. 2003 May-Jun; 11(3):153-6.
- Breinholt V., Larsen J.C. Detection of weak estrogenic flavonoids using a recombinant yeast strain and a modified MCF7 cell proliferation assay. Chem. Res. Toxicol. 1998;11:622–629. doi: 10.1021/tx970170y. [PubMed] [CrossRef] [Google Scholar]
- Kuiper G.G., Lemmen J.G., Carlsson B., Corton J.C., Safe S.H., van der Saag P.T., van der Burg B., Gustafsson J.A. Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinology. 1998;139:4252–4263. doi: 10.1210/endo.139.10.6216. [PubMed] [CrossRef] [Google Scholar]
- Adlercreutz H., Markkanen H., Watanabe S. Plasma concentrations of phyto-oestrogens in Japanese men. Lancet. 1993;342:1209–1210.
- Kapiotis S., Hermann M., Held I., Seelos C., Ehringer H., Gmeiner B.M. Genistein, the dietary-derived angiogenesis inhibitor, prevents LDL oxidation and protects endothelial cells from damage by atherogenic LDL. Arterioscler. Thromb. Vasc. Biol. 1997;17:2868–2874.
- Nilsson S., Gustafsson J.-A. Biological role of estrogen and estrogen receptors. Crit. Rev. Biochem. Mol. Biol. 2002;37:1–28.
- Meegan M.J., Lloyd D.G. Advances in the science of estrogen receptor modulation. Curr. Med. Chem. 2003;10:181–210.
- Riggs B.L., Hartmann L.C. Selective estrogen-receptor modulators—Mechanisms of action and application to clinical practice. N. Engl. J. Med. 2003;348:618–629.
- Smith C.L., O’Malley B.W. Coregulator function: A key to understanding tissue specificity of selective receptor modulators. Endocr. Rev. 2004;25:45–71.
- Liu X.X., Li S.H., Chen J.Z., Sun K., Wang X.J., Wang X.G., Hui R.T. Effect of soy isoflavones on blood pressure: A meta-analysis of randomized controlled trials. Nutr. Metab. Cardiovasc. Dis. 2012;22:463–470.
- Hooper L., Ryder J.J., Kurzer M.S., Lampe J.W., Messina M.J., Phipps W.R., Cassidy A. 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;15:423–440.
- Matthews J., Gustafsson J.-A. Estrogen signaling: A subtle balance between ER alpha and ER beta. Mol. Interv. 2003;3:281–292.
- A model to estimate the oestrogen receptor mediated effects from exposure to soy isoflavones in food. Safford B, Dickens A, Halleron N, Briggs D, Carthew P, Baker V. Regul Toxicol Pharmacol. 2003 Oct; 38(2):196-209.
- Safety of soy-based infant formulas containing isoflavones: the clinical evidence. Merritt RJ, Jenks BH. J Nutr. 2004 May; 134(5):1220S-1224S
- Gu L., House S.E., Prior R.L., Fang N., Ronis M.J.J., Clarkson T.B., Wilson M.E., Badger T.M. Metabolic phenotype of isoflavones differ among female rats, pigs, monkeys, and women. J. Nutr. 2006;136:1215–1221.
- Wisniewski A.B., Klein S.L., Lakshmanan Y., Gearhart J.P. Exposure to genistein during gestation and lactation demasculinizes the reproductive system in rats. J. Urol. 2003;169:1582–1586.
- Fielden M.R., Samy S.M., Chou K.C., Zacharewski T.R. Effect of human dietary exposure levels of genistein during gestation and lactation on long-term reproductive development and sperm quality in mice. Food Chem. Toxicol. 2003;41:447–454.
- Ojeda S.R., Andrews W.W., Advis J.P., White S.S. Recent advances in the endocrinology of puberty. Endocr. Rev. 1980;1:228–257.
- Robinson J.D., Judd H.L., Young P.E., Jones O.W., Yen S.S. Amniotic fluid androgens and estrogens in midgestation. J. Clin. Endocrinol. Metab. 1977;45:755–761.
- Setchell K.D.R., Brown N.M., Zhao X., Lindley S.L., Heubi J.E., King E.C., Messina M.J. Soy isoflavone phase II metabolism differs between rodents and humans: Implications for the effect on breast cancer risk. Am. J. Clin. Nutr. 2011;94:1284–1294.
- Soukup S.T., Helppi J., Müller D.R., Zierau O., Watzl B., Vollmer G., Diel P., Bub A., Kulling S.E. Phase II metabolism of the soy isoflavones genistein and daidzein in humans, rats and mice: A cross-species and sex comparison. Arch. Toxicol. 2016;90:1335–1347.
- A specific breeding problem of sheep on subterranean clover pastures in Western Australia. Bennetts HW, Underwood EJ, Shier FL. Aust Vet J. 1946 Feb; 22(1):2-12
- Hypogonadism and erectile dysfunction associated with soy product consumption. Siepmann T, Roofeh J, Kiefer FW, Edelson DG. Nutrition. 2011 Jul-Aug; 27(7-8):859-62.
- An unusual case of gynecomastia associated with soy product consumption. Martinez J, Lewi JE. Endocr Pract. 2008 May-Jun; 14(4):415-8.
- Review Soybean isoflavone exposure does not have feminizing effects on men: a critical examination of the clinical evidence. Messina M. Fertil Steril. 2010 May 1; 93(7):2095-104.
- Song G., Kochman L., Andolina E., Herko R.C., Brewer K.J., Lewis V. Beneficial effects of dietary intake of plant phytoestrogens on semen parameters and sperm DNA integrity in infertile men. Fertil. Steril. 2006;86:S49.
- Mitchell J.H., Cawood E., Kinniburgh D., Provan A., Collins A.R., Irvine D.S. Effect of a phytoestrogen food supplement on reproductive health in normal males. Clin. Sci. 2001;100:613–618.
- Hamilton-Reeves J.M., Vazquez G., Duval S.J., Phipps W.R., Kurzer M.S., Messina M.J. Clinical studies show no effects of soy protein or isoflavones on reproductive hormones in men: Results of a meta-analysis. Fertil. Steril. 2010;94:997–1007.
- National Toxicology Program Multigenerational reproductive study of genistein (Cas No. 446-72-0) in Sprague-Dawley rats (feed study) Natl. Toxicol. Program Tech. Rep. Ser. 2008;539:1–266
- Review Investigating the role of natural phyto-oestrogens on bone health in postmenopausal women. Valtueña S, Cashman K, Robins SP, Cassidy A, Kardinaal A, Branca F. Br J Nutr. 2003 Jun; 89 Suppl 1():S87-9.
- Review Soy foods and supplementation: a review of commonly perceived health benefits and risks. D’Adamo CR, Sahin A. Altern Ther Health Med. 2014 Winter; 20 Suppl 1():39-51
- Does soy protein affectcirculating levels of unbound IGF-1? Messina M, Magee P. Eur J Nutr. 2018 Mar;57(2):423-432.
- Review Genistein genotoxicity: critical considerations of in vitro exposure dose. Klein CB, King AA. Toxicol Appl Pharmacol. 2007 Oct 1; 224(1):1-11.
- Review Soy, Soy Foods and Their Role in Vegetarian Diets. Rizzo G, Baroni L. Nutrients. 2018 Jan 5; 10(1):.
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