Health Care Professional Information

Scientific Name
Glycine max
Common Name

Soybean, soya, tofu, miso, tempeh

Clinical Summary

Soy is derived from the seed of Glycine max. Soybeans are rich in protein and other essential nutrients and are widely consumed as food. Soy also contains significant amounts of isoflavones — genistein (4',5,7-trihydroxyisoflavone), daidzein (4',7-dihydroxyisoflavone), and glycitein (4',7-dihydroxy-6-methoxyisoflavone) (1). They are marketed as dietary supplements to treat hot flashes, high cholesterol, and for cancer prevention. Isoflavones are thought to exhibit both selective estrogen receptor modulator activity and non-hormonal effects. Studies on the effect of soy for menopausal symptoms are inconclusive (2) (3) (4) (5) (6) (7) (8) (9). While some studies indicate that soy may slow bone density loss, (10) (11) others report no effects on bone mineral density in postmenopausal women (12) (13). Soy was shown to reduce low-density-lipoprotein (LDL)(14) in postmenopausal women (15) and blood pressure in hypertensive postmenopausal women (16), suggesting a benefit for cardiovascular health (17). Genistein also reduced fasting blood glucose and insulin levels as well as improving insulin resistance (18). Soy intake also reduced proteinuria in type 2 diabetic patients with nephropathy (19). However, conflicting data suggest no such protective effects of soy consumption against diabetes (20).

Soy may reduce risk of prostate (21) (22) (23), lung (24) (80), and endometrial (25) (26) cancers, but can increase the risk of bladder cancer (27) and endometrial hyperplasia (28). It was also shown to prevent breast cancer (29) (30) but conflicting data suggest that soy supplementation may have adverse effects (31) (32). A study done in mice suggests that consumption of soy products may increase metastasis (33). Genistein, the most estrogenic soy isoflavone (34), demonstrates antiproliferative effects in multiple cell lines, including breast cancer (ER-positive and negative) (35), prostate cancer (androgen-dependent and independent) (36), nasopharyngeal carcinoma (37), neuroblastoma, sarcoma, and retinoblastoma cells (36). Animal studies also show that genistein antagonizes the effects of tamoxifen (38) (39) and promotes tumor progression in advanced prostate cancer (40). Soy supplement may decrease serum PSA levels in prostate cancer patients before prostatectomy (41), but this effect is not observed in patients after prostatectomy (82) . Further research is needed to evaluate the role of genistein in cancer prevention.

Soy consumption reduced mortality and recurrence in breast cancer patients, regardless of tamoxifen use (42). It also prolongs survival among women with lung cancer (81). Supplementation with soy isoflavones may reduce the adverse effects associated with chemotherapy (43) and radiotherapy (44), but when used together with vitamin E and selenium, did not prevent prostate cancer progression (45). It was also ineffective in reducing hot flashes in patients with prostate cancer (83).

Patients should consult their physicians about the use of soy supplements.

Food Sources

Raw soybeans, low-fat soy flour, roasted soybeans, dry-roasted soy beans, soy milk, tofu, and soy protein isolate. There are no isoflavones in soy sauce or soy oil.

Purported Uses
  • Cancer prevention
  • Cardiovascular disease
  • High cholesterol
  • Menopausal symptoms
  • Osteoporosis
Constituents
  • Isoflavones: Genistein, daidzein, glycitein
  • Glucosides
  • Phospholipids: Phosphatidylcholine, lecithin, linoleic acid, oleic acid
  • Protein
  • Carbohydrate
    (1) (46)
Mechanism of Action

Animal studies suggest that genistein and daidzein have an ability to prevent or reduce bone loss in a manner similar to synthetic estrogen due to increased beta versus alpha estrogen receptor (ER) binding (10). Both isoflavones may modulate bone remodeling through ERs by regulating target gene expression (50). Soy may also contribute to maintaining bone density by causing less calcium to be excreted in the urine (35).

Proposed mechanisms of soy’s cholesterol-lowering effect include phytoestrogen-induced hyperthyroid state and increased excretion of bile acids, which may enhance removal of LDL. Isoflavones may inhibit oxidation of LDL and may alter hepatic metabolism with enhanced removal of LDL and VLDL by hepatocytes (17). Serum lipids may also be regulated through modified transcription factor and downstream gene expression and by promoting antioxidant enzyme activity (51).

The phytochemicals in soybeans also exhibit anticarcinogenic activity, for which many mechanisms have been proposed. Genistein affects microRNA expression—targeted translation inhibitors for multiple proteins implicated in the regulation of various pathobiological processes in cancer (52). In addition, genistein demonstrated an anti-minichromosome maintenance (MCM) effect, a gene family frequently upregulated in various cancers and considered a promising anticancer drug target (53).

In breast cancer, genistein acts as an agonist to estrogen receptor (ER)-alpha in ER-alpha-predominant breast cancer cells, but likely acts as an antiestrogen in cells with ER-beta alone, suggesting therapeutic potential for premenopausal women with ER-alpha-negative/ER-beta-positive tumors (54). However, in an in vitro breast model, genistein also induced estrogen-dependent MCF-7 tumor cell growth and increased breast cancer-associated aromatase expression and activity, suggesting that soy-based supplements may affect the efficacy of aromatase inhibitors used in breast cancer treatment (55). Genistein is also known to negate the inhibitory effect of tamoxifen on MCF-7 tumor growth and increase expression of estrogen-responsive genes (38). Alternatively, soy isoflavones may reduce breast cancer risk by decreasing endogenous ovarian steroid levels (56). Studies suggest that some benefits ascribed to dietary isoflavones may depend on early life exposure, thereby impacting gene expression at an epigenetic level. (47) (48) (49)

In prostate cancer, soy protein extracts appear to influence the progression of established tumors rather than inhibit etiologic factors. Furthermore, soy protein consumption reduces androgen receptor expression in prostate tumors (57). Other proposed prevention mechanisms include genistein-induced prostate cancer cell adhesion, direct growth inhibition, and induction of apoptosis (22). Growth inhibition appears to be independent of genistein’s estrogenic effects. In human prostate cancer cell lines, both genistein and daidzein affect microRNA regulation (58) and induce decreased methylation of gene promoters including BRCA1(59). In tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-resistant prostate cancer cells, soy isoflavones enhance TRAIL-mediated apoptosis by engaging apoptotic pathways and regulating NF-κB activity (60) (61). However, in a patient-derived prostate cancer xenograft model, increased proliferation and metastasis in genistein-treated groups were linked to enhanced activities of tyrosine kinases, the epidermal growth factor receptor, and its downstream Src (40). Both genistein and daidzein also act as radiosensitizers for prostate cancer in vitro and in vivo, but pure genistein increased lymph node metastasis, whereas the combination of genistein, daidzein, and glycitein did not. Daidzein may protect against genistein-induced metastasis, and its ability to inhibit cell growth and potentiate radiation appears to be androgen-receptor-independent (62). In addition, soy isoflavones radiosensitized human A549 NSCLC cells, and decreased hemorrhages, inflammation, and fibrosis caused by radiation suggesting protection of normal lung tissue (63). The combination of genistein, daidzein, and glycitein also mediated growth-suppressive effects via ER-beta in DLD-1 human colon adenocarcinoma cells (64). 7,3’,4’-trihydroxyisoflavone (THIF), a daidzein metabolite, targets Cot and MKK4 to inhibit UVB-induced skin cancer (65) and cyclin-dependent kinases and phosphatidylinositol 3-kinase to inhibit EGF-induced proliferation and transformation in JB6 P+ mouse epidermal cells (66).

The intestinally derived isoflavone metabolite R-equol, but not S-equol, was also found to be potently chemopreventive (67). However, neonatal and prepubertal exposure to equol showed no long-term chemoprevention against DMBA-induced mammary tumors even though an equol-exposure ‘imprinting’ effect resulted in a decrease in immature terminal end structures and an increase in mature lobules (68).

The soy peptide lunasin exhibits chemopreventive properties via gene expression upregulation (69) and cell adhesion (70), apoptosis (71), and anti-inflammatory activity (72).

Pharmacokinetics

Pre-absorption: Prior to absorption, isoflavones undergo extensive metabolism in the intestinal tract. Genistein is formed from biochanin A, and daidzein from formonentin. Genistein, daidzein, and glycitein may be metabolized further to specific metabolites such as equol, O-desmethylangolensis, dihydrogenistein, and p-ethylphenol. Many variables can affect this metabolism. An analysis of phytoestrogen supplements and extracts demonstrated notable differences in isoflavone content as compared with manufacturer claims (73). Qualitative and quantitative differences in plasma concentrations of isoflavones were observed based on the type of supplement used. Such variations in pharmacokinetics and metabolism should be taken into consideration when conducting clinical studies.

Metabolism/Excretion: Following absorption, isoflavones undergo enterohepatic circulation, are secreted into bile, and are eliminated via the kidneys primarily as glucuronide conjugates. However, a portion of isoflavones in the portal blood can escape first-pass liver uptake, entering peripheral circulation. The plasma half-life of genistein and daidzein is approximately 8 hours. In adults, peak concentrations occur in 6 to 8 hours (74).

Warnings

Consumption of home-fermented tofu resulted in two cases of botulism (84).

Contraindications
  • Soy is contraindicated in patients who are hypersensitive to soy products.
Adverse Reactions
  • Flatulence, allergic reactions

Case Reports

  • A 60-year-old man developed gynecomastia following consumption of soy milk over a period of six months. His symptoms resolved after discontinuing soy use (76).
  • Three women experienced abnormal uterine bleeding with endometrial pathology after high intake of soy products. Their symptoms improved following withdrawal of soy use (77).
  • 19-year-old type diabetic but otherwise healthy man experienced sudden onset of loss of libido and erectile dysfunction following consumption of large amounts of soy-based products in a vegan-style diet. His symptoms improved one year after discontinuing the vegan diet (78).
  • A 55-year-old woman died from massive pulmonary edema following consumption of a large quantity of Japanese soy sauce, shoyu (79).
  • A 19-year-old man suffered from a seizure-like activity due to acute hypernatremia, 2 hours after ingesting a quart of soy sauce (85). His symptoms improved following treatment with large quantities of water.
Herb-Drug Interactions
  • Tamoxifen: Animal studies suggest that genistein, a soy isoflavone, may antagonize the effects of tamoxifen on estrogen-dependent breast cancer (MCF-7) (38) (39).
  • Aromatase Inhibitors: Genistein also induced MCF-7 tumor cell growth and increased breast cancer-associated aromatase expression and activity in an in vitro breast model, suggesting that soy-based supplements may affect the efficacy of aromatase inhibitors used in breast cancer treatment (55).
  • Cytochrome P450 substrates: Soymilk and miso were shown to induce CYP3A4 in vivo, and can affect the intracellular concentration of drugs metabolized by this enzyme (86).
  • P-Glycoprotein: Soymilk and miso were shown to induce P-Gp in vivo, and can affect the intracellular concentration of certain drugs (86).
  • UGT (Uridine 5'-diphospho-glucuronosyltransferase) substrates: Soy modulates UGT enzymes in vitro and can increase the side effects of drugs metabolized by them (75).
Literature Summary and Critique

Shu XO, Zheng Y, Cai H, et al. Soy food intake and breast cancer survival. JAMA 2009;302(22):2437-43.
This is a large, population-based cohort study of 5042 female breast cancer survivors conducted in China. Information about cancer diagnosis, treatment, lifestyle changes, and disease progression was collected at 6 months after diagnosis with three follow-up points at 18, 36, and 60 months post diagnosis. The main outcome measures were total mortality and breast cancer recurrence. Researchers observed an inverse association between consumption of soy foods and mortality and recurrence. Further, this association was seen in women with both estrogen receptor-positive or negative breast cancer, regardless of tamoxifen use.
These data suggest that soy intake is safe and can benefit women with breast cancer.

Azadbakht L, Kimiagar M, Mehrabi Y, et al. Dietary soya intake alters plasma antioxidant status and lipid peroxidation in postmenopausal women with the metabolic syndrome. Br J Nutr. 2007;98(4):807-13.
The effect of soy consumption on metabolic syndrome parameters was analyzed in 42 postmenopausal women in this randomized crossover study. Women consumed a control diet, which consisted of the Dietary Approaches to Stop Hypertension (DASH) diet, the DASH diet with soy protein in place of red meat, or the DASH diet with soy nut in place of red meat for 8 weeks each with 4-week washout periods. All the diets reduced fasting blood glucose, LDL cholesterol, total cholesterol, fasting insulin, and insulin resistance (as assessed by the homeostasis model assessment for insulin resistance, HOMA-IR), but the soy nut diet most greatly improved fasting blood glucose levels, HOMA-IR scores, and LDL levels as compared with the soy protein diet, indicating that differences in soy products may influence metabolic syndrome improvements. The authors surmise that greater unsaturated fat and isoflavone content in soy nuts may mediate these improvements.

Schabath M, Hernandez L, Wu X, et al. Dietary phytoestrogens and lung cancer risk. JAMA. 2005;294(12):1493-504.
In a large case-control study that involved over 1,600 lung cancer patients and approximately equal number of healthy controls, the consumption of phytoestrogens has been shown to reduce the risk of lung cancer. High intake of soy isoflavones has the most significant protective effect, 72% for men and 44% for women. It is unclear if life style or dietary variations between groups contributed to this reduction in risk. This is the strongest evidence ever presented to support the use of soy as a chemopreventive agent. However, the authors cautioned against over interpretation of the findings and suggested further large-scale studies to confirm these results.

Kreijkamp-Kaspers S, Kok L, Grobbee DE, et al. Effect of soy protein containing isoflavones on cognitive function, bone mineral density, and plasma lipids in postmenopausal women. JAMA. 2004;292:65-74.
In this double-blind randomized trial, 202 healthy postmenopausal women were randomly administered either 25.6g of soy protein or placebo on a daily basis for 12 months. Subjects who took soy protein did not show any improvement in cognitive function, bone mineral density, or plasma lipids when compared with those who took placebo. Researchers concluded that soy protein does not have any effect on cognitive function, bone mineral density, or plasma lipids in postmenopausal women when started at the age of 60 years or later.

Dosage (Inside MSKCC Only)
This field is only visible to only OneMSK users.
References
  1. Huang KC. The Pharmacology of Chinese Herbs. 2nd ed. New York: CRC Press.
  2. Van Patten CL, Olivotto IA, Chambers GK, et al. Effect of soy phytoestrogens on hot flashes in postmenopausal women with breast cancer: a randomized, controlled clinical trial. J Clin Oncol. Mar 15 2002;20(6):1449-1455.
  3. Cassidy A, Bingham S, Setchell KD. Biological effects of a diet of soy protein rich in isoflavones on the menstrual cycle of premenopausal women. Am J Clin Nutr. Sep 1994;60(3):333-340.
  4. Han KK, Soares JM, Jr., Haidar MA, et al. Benefits of soy isoflavone therapeutic regimen on menopausal symptoms. Obstet Gynecol. Mar 2002;99(3):389-394.
  5. Newton KM, Reed SD, LaCroix AZ, et al. Treatment of vasomotor symptoms of menopause with black cohosh, multibotanicals, soy, hormone therapy, or placebo: a randomized trial. Ann Intern Med. Dec 19 2006;145(12):869-879.
  6. Scambia G, Mango D, Signorile PG, et al. Clinical effects of a standardized soy extract in postmenopausal women: a pilot study. Menopause. Mar-Apr 2000;7(2):105-111.
  7. Upmalis DH, Lobo R, Bradley L, et al. Vasomotor symptom relief by soy isoflavone extract tablets in postmenopausal women: a multicenter, double-blind, randomized, placebo-controlled study. Menopause. Jul-Aug 2000;7(4):236-242.
  8. Brink E, Coxam V, Robins S, et al. Long-term consumption of isoflavone-enriched foods does not affect bone mineral density, bone metabolism, or hormonal status in early postmenopausal women: a randomized, double-blind, placebo controlled study. Am J Clin Nutr. Mar 2008;87(3):761-770.
  9. Jacobs A, Wegewitz U, Sommerfeld C, et al. Efficacy of isoflavones in relieving vasomotor menopausal symptoms - A systematic review. Mol Nutr Food Res. Sep 2009;53(9):1084-1097.
  10. Potter SM, Baum JA, Teng H, et al. Soy protein and isoflavones: their effects on blood lipids and bone density in postmenopausal women. Am J Clin Nutr. Dec 1998;68(6 Suppl):1375S-1379S.
  11. Marini H, Minutoli L, Polito F, et al. Effects of the phytoestrogen genistein on bone metabolism in osteopenic postmenopausal women: a randomized trial. Ann Intern Med. Jun 19 2007;146(12):839-847.
  12. Kreijkamp-Kaspers S, Kok L, Grobbee DE, et al. Effect of soy protein containing isoflavones on cognitive function, bone mineral density, and plasma lipids in postmenopausal women: a randomized controlled trial. JAMA. Jul 7 2004;292(1):65-74.
  13. Alekel DL, Van Loan MD, Koehler KJ, et al. The soy isoflavones for reducing bone loss (SIRBL) study: a 3-y randomized controlled trial in postmenopausal women. Am J Clin Nutr. Jan 2010;91(1):218-230.
  14. Rideout TC, Chan YM, Harding SV, et al. Low and moderate-fat plant sterol fortified soymilk in modulation of plasma lipids and cholesterol kinetics in subjects with normal to high cholesterol concentrations: report on two randomized crossover studies. Lipids Health Dis. 2009;8:45.
  15. Allen JK, Becker DM, Kwiterovich PO, et al. Effect of soy protein-containing isoflavones on lipoproteins in postmenopausal women. Menopause. Jan-Feb 2007;14(1):106-114.
  16. Welty FK, Lee KS, Lew NS, et al. Effect of soy nuts on blood pressure and lipid levels in hypertensive, prehypertensive, and normotensive postmenopausal women. Arch Intern Med. May 28 2007;167(10):1060-1067.
  17. Lissin LW, Cooke JP. Phytoestrogens and cardiovascular health. J Am Coll Cardiol. May 2000;35(6):1403-1410.
  18. Atteritano M, Marini H, Minutoli L, et al. Effects of the phytoestrogen genistein on some predictors of cardiovascular risk in osteopenic, postmenopausal women: a two-year randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab. Aug 2007;92(8):3068-3075.
  19. Azadbakht L, Esmaillzadeh A. Soy-protein consumption and kidney-related biomarkers among type 2 diabetics: a crossover, randomized clinical trial. J Ren Nutr. Nov 2009;19(6):479-486.
  20. Morimoto Y, Steinbrecher A, Kolonel LN, et al. Soy consumption is not protective against diabetes in Hawaii: the Multiethnic Cohort. Eur J Clin Nutr. Feb 2011;65(2):279-282.
  21. Jacobsen BK, Knutsen SF, Fraser GE. Does high soy milk intake reduce prostate cancer incidence? The Adventist Health Study (United States). Cancer Causes Control. Dec 1998;9(6):553-557.
  22. Moyad MA. Soy, disease prevention, and prostate cancer. Semin Urol Oncol. May 1999;17(2):97-102.
  23. Severson RK, Nomura AM, Grove JS, et al. A prospective study of demographics, diet, and prostate cancer among men of Japanese ancestry in Hawaii. Cancer Res. Apr 1 1989;49(7):1857-1860.
  24. Schabath MB, Hernandez LM, Wu X, et al. Dietary phytoestrogens and lung cancer risk. JAMA. Sep 28 2005;294(12):1493-1504.
  25. Horn-Ross PL, John EM, Canchola AJ, et al. Phytoestrogen intake and endometrial cancer risk. J Natl Cancer Inst. Aug 6 2003;95(15):1158-1164.
  26. Goodman MT, Wilkens LR, Hankin JH, et al. Association of soy and fiber consumption with the risk of endometrial cancer. Am J Epidemiol. Aug 15 1997;146(4):294-306.
  27. Sun CL, Yuan JM, Arakawa K, et al. Dietary soy and increased risk of bladder cancer: the Singapore Chinese Health Study. Cancer Epidemiol Biomarkers Prev. Dec 2002;11(12):1674-1677.
  28. Unfer V, Casini ML, Costabile L, et al. Endometrial effects of long-term treatment with phytoestrogens: a randomized, double-blind, placebo-controlled study. Fertil Steril. Jul 2004;82(1):145-148, quiz 265.
  29. Cline JM, Hughes CL, Jr. Phytochemicals for the prevention of breast and endometrial cancer. Cancer Treat Res. 1998;94:107-134.
  30. Butler LM, Wu AH, Wang R, et al. A vegetable-fruit-soy dietary pattern protects against breast cancer among postmenopausal Singapore Chinese women. Am J Clin Nutr. Apr 2010;91(4):1013-1019.
  31. Trock BJ, Hilakivi-Clarke L, Clarke R. Meta-analysis of soy intake and breast cancer risk. J Natl Cancer Inst. Apr 5 2006;98(7):459-471.
  32. Steinberg FM, Murray MJ, Lewis RD, et al. Clinical outcomes of a 2-y soy isoflavone supplementation in menopausal women. Am J Clin Nutr. Feb 2011;93(2):356-367.
  33. Martinez-Montemayor MM, Otero-Franqui E, Martinez J, et al. Individual and combined soy isoflavones exert differential effects on metastatic cancer progression. Clin Exp Metastasis. Oct 2010;27(7):465-480.
  34. Muthyala RS, Ju YH, Sheng S, et al. Equol, a natural estrogenic metabolite from soy isoflavones: convenient preparation and resolution of R- and S-equols and their differing binding and biological activity through estrogen receptors alpha and beta. Bioorg Med Chem. Mar 15 2004;12(6):1559-1567.
  35. Hasler CM, Finn SC. Soy: just a hill of beans? J Womens Health. Jun 1998;7(5):519-523.
  36. Setchell KD. Phytoestrogens: the biochemistry, physiology, and implications for human health of soy isoflavones. Am J Clin Nutr. Dec 1998;68(6 Suppl):1333S-1346S.
  37. Han H, Zhong C, Zhang X, et al. Genistein induces growth inhibition and G2/M arrest in nasopharyngeal carcinoma cells. Nutr Cancer. 2010;62(5):641-647.
  38. Ju YH, Doerge DR, Allred KF, et al. Dietary genistein negates the inhibitory effect of tamoxifen on growth of estrogen-dependent human breast cancer (MCF-7) cells implanted in athymic mice. Cancer Res. May 1 2002;62(9):2474-2477.
  39. Liu B, Edgerton S, Yang X, et al. Low-dose dietary phytoestrogen abrogates tamoxifen-associated mammary tumor prevention. Cancer Res. Feb 1 2005;65(3):879-886.
  40. Nakamura H, Wang Y, Kurita T, et al. Genistein increases epidermal growth factor receptor signaling and promotes tumor progression in advanced human prostate cancer. PloS one. 2011;6(5):e20034.
  41. Lazarevic B, Boezelijn G, Diep LM, et al. Efficacy and safety of short-term genistein intervention in patients with localized prostate cancer prior to radical prostatectomy: a randomized, placebo-controlled, double-blind Phase 2 clinical trial. Nutr Cancer. 2011;63(6):889-898.
  42. Shu XO, Zheng Y, Cai H, et al. Soy food intake and breast cancer survival. JAMA. Dec 9 2009;302(22):2437-2443.
  43. Tacyildiz N, Ozyoruk D, Yavuz G, et al. Soy isoflavones ameliorate the adverse effects of chemotherapy in children. Nutr Cancer. 2010;62(7):1001-1005.
  44. Ahmad IU, Forman JD, Sarkar FH, et al. Soy isoflavones in conjunction with radiation therapy in patients with prostate cancer. Nutr Cancer. 2010;62(7):996-1000.
  45. Fleshner NE, Kapusta L, Donnelly B, et al. Progression from high-grade prostatic intraepithelial neoplasia to cancer: a randomized trial of combination vitamin-E, soy, and selenium. J Clin Oncol. Jun 10 2011;29(17):2386-2390.
  46. Schultz V, Hansel R, Tyler VE. Rational Phytotherapy: A Physician’s Guide to Herbal Medicine. 4th ed. New York: Springer.
  47. Shu XO, Jin F, Dai Q, et al. Soyfood intake during adolescence and subsequent risk of breast cancer among Chinese women. Cancer Epidemiol Biomarkers Prev. May 2001;10(5):483-488.
  48. Wu AH, Wan P, Hankin J, et al. Adolescent and adult soy intake and risk of breast cancer in Asian-Americans. Carcinogenesis. Sep 2002;23(9):1491-1496.
  49. Korde LA, Wu AH, Fears T, et al. Childhood soy intake and breast cancer risk in Asian American women. Cancer Epidemiol Biomarkers Prev. Apr 2009;18(4):1050-1059.
  50. Tang X, Zhu X, Liu S, et al. Isoflavones suppress cyclic adenosine 3',5'-monophosphate regulatory element-mediated transcription in osteoblastic cell line. J Nutr Biochem. Sep 2011;22(9):865-873.
  51. Marsh TG, Straub RK, Villalobos F, et al. Soy protein supports cardiovascular health by downregulating hydroxymethylglutaryl-coenzyme A reductase and sterol regulatory element-binding protein-2 and increasing antioxidant enzyme activity in rats with dextran sodium sulfate-induced mild systemic inflammation. Nutr Res. Dec 2011;31(12):922-928.
  52. American Menopause Society. The role of soy isoflavones in menopausal health: report of The North American Menopause Society/Wulf H. Utian Translational Science Symposium in Chicago, IL (October 2010). Menopause. Jul 2011;18(7):732-753.
  53. Majid S, Dar AA, Saini S, et al. Regulation of minichromosome maintenance gene family by microRNA-1296 and genistein in prostate cancer. Cancer Res. Apr 1 2010;70(7):2809-2818.
  54. Rajah TT, Du N, Drews N, et al. Genistein in the presence of 17beta-estradiol inhibits proliferation of ERbeta breast cancer cells. Pharmacology. 2009;84(2):68-73.
  55. van Duursen MB, Nijmeijer SM, de Morree ES, et al. Genistein induces breast cancer-associated aromatase and stimulates estrogen-dependent tumor cell growth in in vitro breast cancer model. Toxicology. Nov 18 2011;289(2-3):67-73.
  56. Dorsher P, Peng Z. Supportive Cancer Care with Chinese Medicine In: Cho WCS, ed: Springer Netherlands; 2010:55-75.
  57. Hamilton-Reeves JM, Rebello SA, Thomas W, et al. Isoflavone-rich soy protein isolate suppresses androgen receptor expression without altering estrogen receptor-beta expression or serum hormonal profiles in men at high risk of prostate cancer. J Nutr. Jul 2007;137(7):1769-1775.
  58. Rabiau N, Trraf HK, Adjakly M, et al. miRNAs differentially expressed in prostate cancer cell lines after soy treatment. In Vivo. Nov-Dec 2011;25(6):917-921.
  59. Adjakly M, Bosviel R, Rabiau N, et al. DNA methylation and soy phytoestrogens: quantitative study in DU-145 and PC-3 human prostate cancer cell lines. Epigenomics. Dec 2011;3(6):795-803.
  60. Szliszka E, Czuba ZP, Mertas A, et al. The dietary isoflavone biochanin-A sensitizes prostate cancer cells to TRAIL-induced apoptosis. Urol oncol. Jul 29 2011.
  61. Szliszka E, Krol W. Soy isoflavones augment the effect of TRAIL-mediated apoptotic death in prostate cancer cells. Oncol Rep. Sep 2011;26(3):533-541.
  62. Singh-Gupta V, Zhang H, Yunker CK, et al. Daidzein effect on hormone refractory prostate cancer in vitro and in vivo compared to genistein and soy extract: potentiation of radiotherapy. Pharm Res. Jun 2010;27(6):1115-1127.
  63. Hillman GG, Singh-Gupta V, Runyan L, et al. Soy isoflavones radiosensitize lung cancer while mitigating normal tissue injury. Radiother Oncol. Nov 2011;101(2):329-336.
  64. Bielecki A, Roberts J, Mehta R, et al. Estrogen receptor-beta mediates the inhibition of DLD-1 human colon adenocarcinoma cells by soy isoflavones. Nutr Cancer. 2011;63(1):139-150.
  65. Lee DE, Lee KW, Byun S, et al. 7,3',4'-Trihydroxyisoflavone, a metabolite of the soy isoflavone daidzein, suppresses ultraviolet B-induced skin cancer by targeting Cot and MKK4. J Biol Chem. Apr 22 2011;286(16):14246-14256.
  66. Lee DE, Lee KW, Song NR, et al. 7,3',4'-Trihydroxyisoflavone inhibits epidermal growth factor-induced proliferation and transformation of JB6 P+ mouse epidermal cells by suppressing cyclin-dependent kinases and phosphatidylinositol 3-kinase. J Biol Chem. Jul 9 2010;285(28):21458-21466.
  67. Brown NM, Belles CA, Lindley SL, et al. The chemopreventive action of equol enantiomers in a chemically induced animal model of breast cancer. Carcinogenesis. May 2010;31(5):886-893.
  68. Brown NM, Belles CA, Lindley SL, et al. Mammary gland differentiation by early life exposure to enantiomers of the soy isoflavone metabolite equol. Food Chem Toxicol. Nov 2010;48(11):3042-3050.
  69. Galvez AF, Huang L, Magbanua MM, et al. Differential expression of thrombospondin (THBS1) in tumorigenic and nontumorigenic prostate epithelial cells in response to a chromatin-binding soy peptide. Nutr Cancer. May 2011;63(4):623-636.
  70. Dia VP, de Mejia EG. Lunasin induces apoptosis and modifies the expression of genes associated with extracellular matrix and cell adhesion in human metastatic colon cancer cells. Mol Nutr Food Res. Jan 5 2011.
  71. de Mejia EG, Wang W, Dia VP. Lunasin, with an arginine-glycine-aspartic acid motif, causes apoptosis to L1210 leukemia cells by activation of caspase-3. Mol Nutr Food Res. Mar 2010;54(3):406-414.
  72. de Mejia EG, Dia VP. Lunasin and lunasin-like peptides inhibit inflammation through suppression of NF-kappaB pathway in the macrophage. Peptides. Dec 2009;30(12):2388-2398.
  73. Setchell KD, Brown NM, Desai P, et al. Bioavailability of pure isoflavones in healthy humans and analysis of commercial soy isoflavone supplements. J Nutr. Apr 2001;131(4 Suppl):1362S-1375S.
  74. Fair WR, Fleshner NE, Heston W. Cancer of the prostate: a nutritional disease? Urology. Dec 1997;50(6):840-848.
  75. Mohamed ME, Frye RF. Effects of herbal supplements on drug glucuronidation. Review of clinical, animal, and in vitro studies. Planta Med. Mar 2011;77(4):311-321.
  76. Martinez J, Lewi JE. An unusual case of gynecomastia associated with soy product consumption. Endocr Pract. May-Jun 2008;14(4):415-418.
  77. Chandrareddy A, Muneyyirci-Delale O, McFarlane SI, et al. Adverse effects of phytoestrogens on reproductive health: a report of three cases. Complement Ther Clin Pract. May 2008;14(2):132-135.
  78. Siepmann T, Roofeh J, Kiefer FW, et al. Hypogonadism and erectile dysfunction associated with soy product consumption. Nutrition. Jul-Aug 2011;27(7-8):859-862.
  79. Furukawa S, Takaya A, Nakagawa T, et al. Fatal hypernatremia due to drinking a large quantity of shoyu (Japanese soy sauce). J Forensic Leg Med. Feb 2011;18(2):91-92.
  80. Yang WS, Va P, Wong MY, et al. Soy intake is associated with lower lung cancer risk: results from a meta-analysis of epidemiologic studies. Am J Clin Nutr. 2011 Dec;94(6):1575-83.
  81. Gong Yang, Xiao-Ou Shu, Hong-Lan Li, et al. Prediagnosis Soy Food Consumption and Lung Cancer Survival in Women. J Clin Oncol. 2013 Apr 20;31(12):1548-53.
  82. Bosland M, Kato I, Zeleniuch-Jacquotte A, et al. Effect of Soy Protein Isolate Supplementation on Biochemical Recurrence of Prostate Cancer After Radical Prostatectomy A Randomized Trial. JAMA. 2013;310(2):170-178.
  83. Vitolins MZ, Griffin L, Tomlinson WV, Vuky J, Adams PT, Moose D, Frizzell B, Lesser GJ, Naughton M, Radford JE Jr, Shaw EG. Randomized trial to assess the impact of venlafaxine and soy protein on hot flashes and quality of life in men with prostate cancer. J Clin Oncol. 2013 Nov 10;31(32):4092-8.
  84. Centers for Disease Control and Prevention (CDC). Botulism associated with home-fermented tofu in two Chinese immigrants—New York City, March-April 2012. MMWR Morb Mortal Wkly Rep. 2013 Jul 5;62(26):529-32.
  85. Carlberg DJ, Borek HA, Syverud SA, Holstege CP. Survival of acute hypernatremia due to massive soy sauce ingestion. J Emerg Med. 2013 Aug;45(2):228-31.
  86. Yu CP, Hsieh YW, Lin SP, Chi YC, Hariharan P, Chao PD, Hou Y. Potential modulation on P-glycoprotein and CYP3A by soymilk and miso: in vivo and ex-vivo studies. Food Chem. 2014 Apr 15;149:25-30.

Consumer Information

How It Works

Bottom Line: Whether soy helps relieve menopausal symptoms is still unclear. It may reduce risk of some cancers.

Soy contains large amounts of substances known as isoflavones, also called phytoestrogens. These substances act in a similar way as estrogen in the body and may also be antioxidants. The effects of soy are weak in younger women because estrogen is abundant. At menopause, however, the effects of soy may increase due to the decrease in estrogen. Studies in animals suggest that soy can prevent or reduce bone loss by acting like estrogen and by reducing loss of calcium.

In laboratory studies, soy isoflavones slowed down the growth of several different types of cancer cells, including breast and prostate cancers. Animal studies showed that genistein, one of the isoflavones, may interfere with tamoxifen that is used for breast cancer. But a new study showed that soy foods can benefit women with breast cancer.

Patients should consult their physicians about use of soy supplements.

Purported Uses
  • To prevent cancer
    Laboratory and some clinical studies suggest that women with high soy intake have a lower risk of developing breast cancer. High intake of soy isoflavones can also reduce risk of lung cancer.
  • To prevent heart disease
    Clinical trials show that soy protein (not soy pills) reduces LDL (bad) cholesterol levels, which may help prevent heart disease.
  • To reduce high cholesterol
    Clinical trials show that soy protein (not soy pills) reduces LDL (bad) cholesterol levels and may increase HDL (good) cholesterol levels.
  • To treat menopause symptoms such as hot flashes, vaginal dryness, sleep disturbances, mood problems
    Clinical studies have conflicting results.
  • To prevent bone loss (osteoporosis)
    Some clinical trials and animal studies support this use.
Research Evidence

Menopausal symptoms
In a clinical trial of post-menopausal breast cancer patients with hot flashes, 59 patients drank 250 ml of soy milk twice daily (containing 90 mg of isoflavones) while 64 patients drank 250 ml placebo rice milk for 12 weeks. Both groups experienced a similar decrease in hot flashes, around 60%, showing that soy milk works no better than placebo in reducing hot flashes. However, patients were allowed to use other therapies and medicines to treat their hot flashes, which may have interfered with the study's results.

Cholesterol levels and bone density
In a study of the effect of diet and soy intake on cholesterol and bone density, 66 patients with high cholesterol followed a low-fat, low-cholesterol diet (“Step 1 diet”) for two weeks. At this point, patients were split into three groups and for six months followed either: 1) the Step 1 diet with 40 g of placebo protein daily, 2) the Step 1 diet with 40 g of low-isoflavone soy protein daily, or 3) the Step 1 diet with 40 g of high-isoflavone soy protein. HDL (“good”) cholesterol rose in groups 2 and 3, but total cholesterol did not decrease. Group 3 had a large increase in bone mineral content compared to group 1.

Breast cancer prevention
In a case-control study, 144 women with newly diagnosed breast cancer were matched (by age, where they lived, etc.) with women without breast cancer. Their intake of phytoestrogens was monitored. Women who consumed a high level of phytoestrogens had a lower risk of developing both premenopausal and postmenopausal breast cancer.

In a large, population-based cohort study of 5042 female breast cancer survivors conducted in China, information about cancer diagnosis, treatment, lifestyle changes, and disease progression was collected at 6 months after diagnosis with three follow-up points at 18, 36, and 60 months. Researchers observed that consumption of soy foods reduced the risk of mortality and breast cancer recurrence. Further, this association was seen in women with both estrogen receptor-positive or negative breast cancer, regardless of tamoxifen use.
These data suggest that soy intake is safe and can benefit women with breast cancer.

Lung cancer prevention
In a large case-control study of 1674 lung cancer patients and 1735 healthy controls, high soy isoflavone intake has been shown to lower the risk of lung cancer by 61%.

Patient Warnings

Consumption of home-fermented tofu resulted in two cases of botulism.

Do Not Take If
  • You are hypersensitive to soy products.
  • You are taking Tamoxifen: Animal studies have shown that genistein, a soy isoflavone, may antagonize the effects of tamoxifen on estrogen-dependent breast cancer.
  • You are taking drugs that are substrates of UGT (Uridine 5'-diphospho-glucuronosyltransferase) enzymes (Soy may increase the risk of side effects of these drugs).
  • You are taking aromatase Inhibitors: Soy-based supplements may affect the efficacy of aromatase inhibitors used in breast cancer treatment.
  • You are taking drugs that are substrates of Cytochrome P450: Soymilk and miso may make them less effective.
  • You are taking drugs that are substrates of P-Glycoprotein: Soymilk and miso may make them less effective.
  • You are taking drugs that are substrates of UGT (Uridine 5'-diphospho-glucuronosyltransferase): Soy can increase the side effects of these drugs.
Side Effects
  • Flatulence
  • Allergic reactions
  • Case Reports
  • A 60-year-old man developed gynecomastia following consumption of soy milk over a period of six months. His symptoms resolved after discontinuing soy use.
  • Three women experienced abnormal uterine bleeding with endometrial pathology after high intake of soy products. Their symptoms improved following withdrawal of soy use.
  • A 19-year-old type diabetic but otherwise healthy man experienced sudden onset of loss of libido and erectile dysfunction following consumption of large amounts of soy-based products in a vegan-style diet. His symptoms improved one year after discontinuing the vegan diet.
  • A 55-year-old woman died from salt poisoning following consumption of a large quantity of Japanese soy sauce, shoyu.
  • A 19-year-old man suffered from a seizure-like activity due to acute hypernatremia, 2 hours  after ingesting a quart of soy sauce.
E-mail your questions and comments to aboutherbs@mskcc.org.