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?
What is it used for?
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?
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®).
For Healthcare Professionals
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 to prevent cancer. 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 reduces low density lipoprotein (LDL) cholesterol (14) (15) along with having beneficial effects on blood pressure in postmenopausal women (16) (97) and in healthy adults (90). A meta-analysis confirmed that consumption of soy leads to reductions in both total cholesterol and LDL in adults (99), and fermented soy products were inversely associated with the risk of cardiovascular disease in women (104).
Soy intake also reduced proteinuria in type-2 diabetic patients with nephropathy (19). But 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); lactobacillus-fermented soy was found to enhance cognitive function in subjects with mild cognitive impairment (100); and supplementation combined with exercise improved cognitive function in elderly adults (103). In a study of chronic stroke patients, ingesting soy milk immediately following rehabilitation exercise improved functional outcomes (101); and consumption along with a low-calorie diet had beneficial effects on some metabolic parameters in patients with non-alcoholic fatty liver disease (102).
Soy has been investigated for its anticancer effects as well. Findings suggest that it may reduce the risk of prostate cancer (21) (22) (23), although high intake of soy and isoflavones was associated with increased risk of mortality (105). Soy may also reduce the risk of lung (24) (80) and endometrial (25) (26) cancers, but can increase the risk of bladder cancer (27) and endometrial hyperplasia (28). No association was found between soy and risk of liver (106) or colorectal (107) cancers.
Soy 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). But a large population-based study found that fermented soy foods may only decrease the risk of non-localized breast cancer, not the overall risk (108). Further, long-term supplementation did not affect mammographic density in breast cancer patients or in 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 indicate 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), has been reported to improve fasting blood glucose, insulin levels, and insulin resistance in postmenopausal women (18). It also 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). Supplementation may also decrease serum PSA levels in prostate cancer patients before (41); but not after prostatectomy despite long-term consumption (82) and secondary analysis of data from this study revealed that it did not affect major cardiovascular risk factors nor exert any adverse effects on thyroid function (110).
Isoflavone supplementation may reduce side effects associated with chemo- or radiotherapy (43) (44), but when used with vitamin E and selenium, does not prevent prostate cancer progression (45). It was also ineffective in reducing hot flashes in patients with prostate cancer (83); and did not modulate risk factors of breast cancer in pre- or postmenopausal women (111). Patients should consult their physicians about the use of soy supplements, whose long-term safety remains to be determined.
Mechanism of Action
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).
- Flatulence, allergic reactions
- Severe hypothyroidism: In a 72-year-old woman with chronic thyroid disease who consumed a health drink that contained soy isoflavone powder extracts, for 6 months (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).
- Fatal acute hypernatremia: In a 40-year-old woman due to massive intake of seasoning soy sauce (109).
- Acute pancreatitis: In a woman in her 40s due to ingesting large amounts of soymilk. Symptoms resolved after discontinuing use (112).
- Tamoxifen: Animal studies suggest that genistein may antagonize the effects of tamoxifen on estrogen-dependent breast cancer (MCF-7) (38) (39). 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 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). Clinical relevance is not known.
- P-Glycoprotein: Soymilk and miso were shown to induce P-Gp in vivo, and can affect the intracellular concentration of certain drugs (86). Clinical relevance is not known.
- Uridine 5’-diphospho-glucuronosyltransferase (UGT) substrates: Soy modulates UGT enzymes in vitro and can increase the side effects of drugs metabolized by them (75). Clinical relevance is not known.
- 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).