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Soy

Soy

Common Names

  • Soybean
  • Soya
  • Tofu
  • Miso
  • Tempeh

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For Patients & Caregivers

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

Soy is a plant that is grown worldwide. The beans are rich in protein and other nutrients and are widely consumed as food. Extracts are sold as dietary supplements to treat hot flashes, high cholesterol, and for cancer prevention. Soy contains large amounts of isoflavones that act like estrogen in the body. Studies in animals suggest that soy can prevent or reduce bone loss. In laboratory studies, 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.

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  • 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 isoflavones may also reduce risk of lung cancer.
  • To prevent heart disease
    Clinical trials show that soy protein, not pills, reduces LDL (bad) cholesterol levels, which may help prevent heart disease.
  • To reduce high cholesterol
    Clinical trials show that soy protein, not 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
    Some clinical trials and animal studies support this use.
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  • You are hypersensitive to soy products.
  • You are taking tamoxifen: Animal studies have shown that genistein may reduce the effects of tamoxifen on estrogen-dependent breast cancer.
  • You are taking aromatase Inhibitors: Soy-based supplements may reduce the effects of aromatase inhibitors used in breast cancer treatment.
  • You are taking cytochrome P450 substrate drugs: Soymilk and miso may make them less effective.
  • You are taking P-Glycoprotein substrate drugs: Soymilk and miso may make them less effective.
  • You are taking UGT (Uridine 5’-diphospho-glucuronosyltransferase) substrate drugs: Soy can increase the side effects of these drugs.
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  • Flatulence
  • Allergic reactions

Case Reports

  • Underactive thyroid: In a 72-year-old woman who had chronic thyroid disease. She had taken a health drink containing soy isoflavones for 6 months. Symptoms improved with medical treatment and discontinuation of the health drink.
  • Breast enlargement: In a 60-year-old man following consumption of soy milk over a period of 6 months. Symptoms resolved after discontinuing use.
  • Abnormal uterine bleeding: In 3 women after a high intake of soy products. Symptoms improved following withdrawal of use.
  • Loss of sex drive and erectile dysfunction: In a 19-year-old diabetic man who was otherwise healthy, following intake of large amounts of soy-based products in a vegan-style diet. Symptoms improved 1 year after discontinuing the diet.
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The isoflavone content is minimal in soy sauce or soy oil.

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For Healthcare Professionals

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Glycine max
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Soybeans, derived from Glycine max, 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 exhibit both selective estrogen receptor modulator activity and non-hormonal effects. Studies of soy for menopausal symptoms are inconclusive (2) (3) (4) (5) (6) (7) (8) (9). While some trials indicate slower bone density loss (10) (11) (91), others report no such effects in postmenopausal women (12) (13). But there may be cardiovascular benefits (17), as soy reduced low-density-lipoprotein (LDL) (14) (15) and had beneficial effects on blood pressure in postmenopausal women (16) (97) and healthy adults (90). Genistein improved fasting blood glucose, insulin levels, and insulin resistance (18).

Soy intake also reduced proteinuria in type 2 diabetic patients with nephropathy (19). However, conflicting data suggest no protective effects against diabetes (20). Other studies of soy did not find benefit for Alzheimer’s disease (92) or for poorly controlled asthma (93), but soy isoflavone supplementation alone or with Vitamin D improved some symptoms and quality of life in patients with irritable bowel disease (94).

Soy has been investigated for its anticancer effects. Data show that it may reduce risk of prostate (21) (22) (23), lung (24) (80), and endometrial (25) (26) cancers, but increase the risk of bladder cancer (27) and endometrial hyperplasia (28). It may prolong survival among women with lung cancer (81), reduce mortality (89) and breast cancer recurrence regardless of tamoxifen use (42), or prevent breast cancer (29) (30). However, long-term soy supplementation did not affect mammographic density in breast cancer patients or high-risk women (95) and other data suggest adverse effects (31) (32) or that supplementation can stimulate over-expression of breast cancer genes in patients with invasive breast cancer (87). Preclinical findings also suggest that soy consumption may increase metastasis (33), and daidzin-rich extracts can promote ER-positive breast cancer growth (88).

Genistein, the most estrogenic isoflavone (34), demonstrated antiproliferative effects in multiple cell lines, including breast cancer (ER+/-) (35), prostate cancer (androgen-dependent/-independent) (36), nasopharyngeal carcinoma (37), neuroblastoma, sarcoma, and retinoblastoma cells (36). However, animal studies show that it antagonizes the effects of tamoxifen (38) (39) and promotes tumor progression in advanced prostate cancer (40). Soy supplements may decrease serum PSA levels in prostate cancer patients before (41), but not after (82), prostatectomy. Further research is needed to evaluate the role of genistein in cancer prevention.

Isoflavone supplementation may reduce side effects associated with chemo- or radiotherapy (43) (44), but when used 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.

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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.

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  • Cancer prevention
  • Cardiovascular disease
  • High cholesterol
  • Menopausal symptoms
  • Osteoporosis
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Animal studies suggest that genistein and daidzein can 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). Isoflavones may inhibit oxidation of LDL and 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).

In addition, several mechanisms have been proposed for soy’s anticancer effects. Genistein affects microRNA expression-targeted translation inhibitors for multiple proteins implicated in regulating various pathobiological processes (52). It also 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 cells, genistein acts as an agonist to estrogen receptor (ER)-alpha in ER-alpha-predominant 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, genistein induces estrogen-dependent MCF-7 tumor cell growth and increases breast cancer-associated aromatase expression/activity, suggesting that soy-based supplements may affect aromatase inhibitor efficacy (55). Genistein is also known to negate tamoxifen’s inhibitory effect 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 the epigenetic level (47) (48) (49).

In prostate tumors, soy protein was shown to reduce androgen receptor expression (57). 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).

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  • Contraindicated in patients who are hypersensitive to soy products.
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  • Flatulence, allergic reactions

Case Reports

  • Severe hypothyroidism: In a 72-year-old woman with chronic thyroid disease who consumed a health drink for 6 months that contained soy isoflavone powder extracts (96).
  • Gynecomastia: In a 60-year-old man following consumption of soy milk over a period of 6 months. Symptoms resolved after discontinuing use (76).
  • Abnormal uterine bleeding: With endometrial pathology in 3 women after a high intake of soy products. Symptoms improved following withdrawal of use (77).
  • Loss of libido and erectile dysfunction: In a 19-year-old diabetic man who was otherwise healthy, following intake of large amounts of soy-based products in a vegan-style diet. Symptoms improved 1 year after discontinuing the diet (78).
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  • Tamoxifen: Animal studies suggest that genistein may antagonize the effects of tamoxifen on estrogen-dependent breast cancer (MCF-7) (38) (39). Relevance in humans has yet to be determined.
  • Aromatase inhibitors: Genistein induced MCF-7 tumor cell growth and increased breast cancer-associated aromatase expression and activity, in vitro, 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 may 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).
  • Uridine 5’-diphospho-glucuronosyltransferase (UGT) substrates: Soy modulates UGT enzymes in vitro and can increase the side effects of drugs metabolized by them (75).
  • Membrane organic anion-transporting polypeptides (OATPs): Soy isoflavones and their metabolites were shown to affect transport of drugs across tissue barriers via human OATP2B1, in vitro. Clinical relevance is not known (98).
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  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.

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  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.

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  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.

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  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.

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  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.

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  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.

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  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.

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  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.

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  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.

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  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.

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  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.

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