Soy has become a ubiquitous ingredient in processed foods and it is especially prevalent in infant formula and as a protein alternative for those who don’t eat animal protein or are sensitive to dairy. Many people, including the medical establishment and health and nutrition associations, consider it a health food. Approximately 25% of infants in the US are fed soy based formulas primarily due to the perceived health benefits rather than due to colic or cow’s milk allergy.1 Besides the risk soy poses to those with IgE mediated allergies to soy and/or legumes, high intake of soy products can carry health risks for certain populations.
Soy is touted as having health benefits such as reduced risk for symptoms of menopause and lower risk of developing heart disease, breast cancer, and osteoporosis and people are often urged to eat more soy products; however, soy phytoestrogens, also called isoflavones, are weak estrogen agonists/antagonists with chemical properties similar to synthetic Bisphenol A (BPA) and as such can be classified as endocrine disruptors.1 Increasingly, research suggests that phytoestrogens can contribute to the development of some cancers, reproductive dysfunction, immune dysfunction, and thyroid disease. Any health benefits of soy phytoestrogens are likely dependent upon age, ethnicity, sex, health status, and gut microbiota.
Phytoestrogens appear to have the most negative impact on human reproductive health when exposed to high levels prior to adolescence, including in the womb.1 Early studies assumed that plasma circulation of soy isoflavones in infants fed soy based formulas that are 13,000-22,000-fold higher than plasma estradiol in breast fed or cow’s milk formula fed infants imparted health benefits later in life such as the prevention of heart disease or cancer; later studies question that assumption.1,2 High soy intake in girls prior to puberty result in greater breast density after puberty; breast density is a risk factor for breast cancer.1 One study found breast bud development in girls as young as 2 years old among infants fed soy formula, leading to questions about the role phytoestrogens play in early puberty and the development of breast cancer later in life, while another study found central precocious puberty in Korean girls ages 8-10 who consumed high amounts of soy.1,3 A small study comparing DNA methylation in vaginal cells between infant girls fed soy formula and cow’s milk formula found decreased expression of an estrogen-responsive gene in those fed soy formula which may result in changes in the reproductive system later in life.4 Infant exposure to phytoestrogens in soy formula has also been connected to both early menarche (≤10 years) and late menarche (14 years); early first occurrence of menstruation is associated with increased risk for breast cancer, endometrial cancer, and menstrual problems.5,6,7 Male fetal development may also be effected by a maternal diet high in soy, with one study indicating a higher incidence of hypospadias, where the urethra develops on the underside of the penis.8 Retrospective studies on adult women who were fed soy formula as infants found an association between longer menstrual bleeding, greater dysmenorrhea, and earlier development of uterine fibroids.8
To further confuse the issue, clinical trials of supplemental soy phytoestrogen in pre-menopausal Caucasian women found that it increased breast density while having no effects on the risk of developing breast cancer, while soy phytoestrogens in pre-menopausal Chinese women significantly reduced risk of developing breast cancer.1 This may be due to differences in genetics, as some estrogen receptor polymorphisms respond better to soy phytoestrogens than others.9
Autoimmune diseases arise due to a confluence of genetics, environment, and random chance; however, the prevalence of women in autoimmune diseases also points to sex hormones, particularly estrogen, playing a role in their development.10 All immune cells contain estrogen receptors that help regulate immune responses. Endocrine disruptors such as phytoestrogens found in soy have the ability to bind to estrogen receptors and change function, including alter gene activity, inhibit natural hormones from binding to the receptors, and increase hormone activity, which can have significant effects on the immune system.10 Genistein, one of the phytoestrogens found in soy, exhibits dose dependent suppression of cell-mediated and humoral immune responses, while other phytoestrogens appear to stimulate immune function.10 Due to these immune effects, it’s possible for phytoestrogens to cause impaired immune function throughout ones life. Studies on children with autoimmune thyroiditis and type I diabetes found higher incidents of both autoimmune diseases in those who were fed soy formula compared to breast milk, and 2.5 times more of the formula-fed children with type I diabetes had positive thyroid antibodies.11,12 Currently there are not enough human trials on the effects of phytoestrogens on the immune system to say whether they increase the occurrence of autoimmune diseases in adults or not.10 Like with reproductive health and cancer risk, there are a lot of variables that need to be considered.
The effects of soy on the thyroid are well-documented; soy is one of a long list of goitrogenic foods, foods that increase the incidence of thyroid goiters.1 The phytoestrogens in soy inhibit thyroid peroxidase (TPO), the enzyme required for the production of thyroid hormones, when iodine is insufficient.13 Inhibition of TPO can lead to thyroid goiter and hypothyroidism. Thankfully, adequate iodine intake reduces the negative effects of soy on the thyroid, though, as with any food, it shouldn’t be consumed within one hour of thyroid medication as it reduces absorption of the medication.
The conclusion of one review article states, “Women who are pregnant, nursing, or attempting to become pregnant should use soy foods with caution and be aware that soy formula may not be the best option for their babies.”1 I would add to that, anyone with estrogen sensitive diseases (including cancers, endometriosis, and uterine fibroids), autoimmune diseases, and thyroid disease should use caution when consuming soy or using soy phytoestrogen or isoflavone supplements.
1. Patisaul HB, Jefferson W. The pros and cons of phytoestrogens. Front Neuroendocrinol. 2010; 31(4): 400-419. doi: 10.1016/j.yfrne.2010.03.003
2. Setchell KD, Zimmer-Nechemias L, Cai J, Heubi JE. Isoflavone content of infant formulas and the metabolic fate of these phytoestrogens in early life. Am J Clin Nutr. 1998; 68(6 Suppl): 1453S-1461S. doi: 10.1093/ajcn/68.6.1453S.
3. Kim J, Kim S, Huh K, Kim Y, Joung H, Park M. High serum isoflavone concentrations are associated with the risk of precocious puberty in Korean girls. Clin Endocrinol (Oxf). 2011; 75(6): 831-835. doi: 10.1111/j.1365-2265.2011.04127.
4. Harlid S, Adgent M, Jefferson WN, Panduri V, Umbach DM, Xu Z, et al. Soy Formula and Epigenetic Modifications: Analysis of Vaginal Epithelial Cells from Infant Girls in the IFED Study. Environ Health Perspect. 2017; 125(3): 447-452. doi: 10.1289/EHP428.
5. Adgent MA, Daniels JL, Rogan WJ, Adair L, Edwards LJ, Westreich D, et al. Early-life soy exposure and age at menarche. Paediatr Perinat Epidemiol. 2012; 26(2): 163-175. doi: 10.1111/j.1365-3016.2011.01244.
6. D’Aloisio AA, DeRoo LA, Baird DD, Weinberg CR, Sandler DP. Prenatal and infant exposures and age at menarche. Epidemiology. 2013; 24(2): 277-284. doi: 10.1097/EDE.0b013e31828062b7.
7. Mishra GD, Cooper R, Tom SE, Kuh D. Early life circumstances and their impact on menarche and menopause. Womens Health (Lond Engl). 2009; 5(2): 175-190. doi:10.2217/17455057.5.2.175.
8. Cederroth CR, Auger J, Zimmermann C, Eustache F, Nef S. Soy, phyto-oestrogens and male reproductive function: a review. Int J Androl. 2010; 33(2): 304-316. doi: 10.1111/j.1365-2605.2009.01011.
9. Iwasaki M, Hamada GS, Nishimoto IN, Netto MM, Motola J Jr, Laginha FM, et al. Isoflavone, polymorphisms in estrogen receptor genes and breast cancer risk in case-control studies in Japanese, Japanese Brazilians and non-Japanese Brazilians. Cancer Sci. 2009;100(5): 927-933. doi: 10.1111/j.1349-7006.2009.01118.
10. Pierdominici M, Ortona E. Estrogen Impact on Autoimmunity Onset and Progression: the Paradigm of Systemic Lupus Erythematosus. International Trends in Immunity. 2013; 1(2): 24-34.
11. Fort P, Lanes R, Dahlem S, Recker B, Weyman-Daum M, Pugliese M, et al. Breast feeding and insulin-dependent diabetes mellitus in children. J Am Coll Nutr. 1986; 5(5): 439-441.
12. Fort P, Moses N, Fasano M, Goldberg T, Lifshitz F. Breast and soy-formula feedings in early infancy and the prevalence of autoimmune thyroid disease in children. J Am Coll Nutr. 1990; 9(2): 164-167.
13. Messina M, Redmond G. Effects of soy protein and soybean isoflavones on thyroid function in healthy adults and hypothyroid patients: a review of the relevant literature. Thyroid. 2006; 16(3): 249-258.