Soy

Purported Benefits, Side Effects & More
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Soy

Common Names

  • Soybean
  • Soya
  • Tofu
  • Miso
  • Tempeh

For Patients & Caregivers

Tell your healthcare providers about any dietary supplements you’re taking, such as herbs, vitamins, minerals, and natural or home remedies. This will help them manage your care and keep you safe.


What is it?

Soybeans are rich in protein and other important nutrients. Soy is found in foods such as tofu, miso, soy sauce, and tempeh. It contains large amounts of substances known as isoflavones that help treat hot flashes and lower high cholesterol. Isoflavones can also help prevent cancer.

What are the potential uses and benefits?

Soy may be useful for:

  • Preventing cancer
  • Preventing heart disease
  • Lowering high cholesterol
  • Preventing bone loss
  • Managing symptoms caused by menopause (permanent end of menstrual cycles), such as hot flashes

Soy also has other uses that haven’t been studied by doctors to see if they work.

It’s generally safe to use soy in food. Talk with your healthcare providers before taking supplements or higher amounts of soy. Herbal supplements are stronger than the herbs you would use in cooking.

Supplements can also interact with some medications and affect how they work. For more information, read the “What else do I need to know?” section below.

What are the side effects?

Side effects of using soy may include:

  • Gas
  • Allergic reactions, such as rashes or hives
What else do I need to know?
  • Talk with your healthcare provider if you’re taking tamoxifen (such as Nolvadex® or Soltamox™). Soy supplements can affect how it works.
  • Talk with your healthcare provider if you’re taking aromatase inhibitors. Aromatase inhibitors are medications that stop an enzyme called aromatase from changing other hormones into estrogen. Some examples of aromatase inhibitors include letrozole (Femara®) and anastrozole (Arimidex®).
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For Healthcare Professionals

Scientific Name
Glycine max
Clinical Summary

Soybeans are rich in protein and other essential nutrients and are widely consumed as food. Soy also contains significant amounts of isoflavones including genistein, daidzein, and glycitein. They are marketed as dietary supplements for hot flashes, high cholesterol, cardiovascular health, and cancer prevention.

Soy isoflavones exhibit both selective estrogen receptor modulator activity and non-hormonal effects. Studies are mixed on whether soy can relieve menopausal symptoms (1) (2) (3) (4) (5) or slow bone loss (6) (7) (8) (9). Other analyses suggest no protective effects against diabetes (10), and lack of benefit in patients with Alzheimer’s disease (11) or poorly controlled asthma (12). However, there may be cardiovascular benefits with soy products (13) (14) as studies show soy intake lowers blood pressure (15) and cholesterol levels (16).

Soy has also been evaluated for anticancer effects. Although it may reduce risk of prostate (17) (18), lung (19) (20), and endometrial (21) (22) cancers, high or prolonged intakes may increase risk of bladder cancer (23), endometrial hyperplasia (24), and mortality (25). Prior soy intake was associated with prolonged survival among women with lung cancer (26), but no associations were found between soy and risk of liver (27) or colorectal (28) cancers.

Studies in breast cancer patients are mixed. Although it may help prevent breast cancer (29) or recurrence (30), or reduce mortality (31), soy intake or supplementation did not modulate risk (32), decrease overall risk (33), or affect mammographic density (34). Other data suggest potential adverse effects (35) (36) or that supplementation can stimulate overexpression of breast cancer genes in some patients (37).

Soy supplementation was also not helpful against prostate cancer progression (38), for high-risk patients post-surgery (39) (40), or for treatment-related hot flashes (41). Other limited data suggest isoflavone supplementation may reduce some side effects from radiation or chemotherapy (42) (43), but larger studies are needed.

Preclinical data suggest higher intakes of soy or specific isoflavones may promote growth or metastasis (44) (45) (46) or antagonize the effects of tamoxifen (47) (48). Patients should consult their physicians about the use of soy supplements, whose long-term safety remains to be determined.

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 and Benefits
  • Cancer
  • Cardiovascular disease
  • High cholesterol
  • Osteoporosis
  • Menopausal symptoms
Mechanism of Action

Soy isoflavones may modulate bone remodeling via estrogen receptors (ER) by regulating target gene expression (49). Isoflavones may inhibit LDL oxidation and alter hepatic metabolism with enhanced removal of LDL and VLDL by hepatocytes (13). Serum lipids may also be regulated via modified transcription factor and downstream gene expression and by promoting antioxidant enzyme activity (50).

Various 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 (51). It also demonstrated an anti-minichromosome maintenance effect, a gene family upregulated in various cancers and considered a promising drug target (52).

In breast cancer cells, genistein acts as an agonist 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 (53). 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 (54). Genistein is also known to negate tamoxifen’s inhibitory effect on MCF-7 tumor growth and increase expression of estrogen-responsive genes (47). Some benefits ascribed to dietary isoflavones may depend on early life exposure, thereby impacting gene expression at the epigenetic level (55).

In prostate tumors, soy protein reduced androgen receptor expression (56). Both genistein and daidzein affect microRNA regulation (57) and induce decreased methylation of gene promoters including BRCA1 (58). In TNF-related apoptosis-inducing ligand-resistant prostate cancer cells, soy isoflavones enhance TRAIL-mediated apoptosis by engaging apoptotic pathways and regulating NF-κB activity (59). 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, EGFR, and its downstream Src (45). Both genistein and daidzein also act as radiosensitizers for prostate cancer, 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 (60). In addition, soy isoflavones radiosensitized human A549 NSCLC cells, and decreased hemorrhages, inflammation, and fibrosis caused by radiation suggesting protection of normal lung tissue (61).

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

Case Reports
Severe hypothyroidism: In a 72-year-old woman with thyroid disease who consumed a health drink containing soy isoflavone extracts for 6 months (62).
Gynecomastia: In a 60-year-old man following 6 months of soy milk consumption (63).
Abnormal uterine bleeding: With endometrial pathology in 3 women after a high intake of soy products (64).
Loss of libido, erectile dysfunction: In a 19-year-old diabetic man following intake of large amounts of soy-based products in a vegan-style diet (65).
Acute pancreatitis: In a woman in her 40s due to ingesting large amounts of soymilk (66).

Herb-Drug Interactions

Tamoxifen: Animal studies suggest genistein may antagonize tamoxifen effects on estrogen-dependent breast cancer (MCF-7) (47) (48). Clinical relevance 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 treatment efficacy (54).
CYP450 substrates: Soymilk and miso induced CYP3A4 in vivo, and may affect the intracellular concentration of drugs metabolized by this enzyme (67). Clinical relevance is not known.
P-Glycoprotein: Soymilk and miso induced P-Gp in vivo, and can affect the intracellular concentration of certain drugs (67). Clinical relevance is not known.
UGT substrates: Soy modulates UGT enzymes in vitro and can increase the side effects of drugs metabolized by them (68). Clinical relevance is not known.
Membrane organic anion-transporting polypeptides (OATPs): Soy isoflavones and their metabolites affected drug transport across tissue barriers via human OATP2B1 in vitro. Clinical relevance is not known (69).

Dosage (OneMSK Only)
References
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  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. Pawlowski JW, Martin BR, McCabe GP, et al. Impact of equol-producing capacity and soy-isoflavone profiles of supplements on bone calcium retention in postmenopausal women: a randomized crossover trial. Am J Clin Nutr. Sep 2015;102(3):695-703.
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  23. 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.
  24. 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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  29. 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.
  30. Shu XO, Zheng Y, Cai H, et al. Soy food intake and breast cancer survival. JAMA. Dec 9 2009;302(22):2437-2443.
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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.
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  47. 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.
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  49. 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.
  50. 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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  52. 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.
  53. 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.
  54. 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.
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  56. 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.
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  61. 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.
  62. Nakamura Y, Ohsawa I, Goto Y, et al. Soy isoflavones inducing overt hypothyroidism in a patient with chronic lymphocytic thyroiditis: a case report. J Med Case Rep. Sep 5 2017;11(1):253.
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  69. Navrátilová L, Applová L, Horký P, et al. Interaction of soy isoflavones and their main metabolites with hOATP2B1 transporter. Naunyn Schmiedebergs Arch Pharmacol. Oct 2018;391(10):1063-1071.
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