SOY ISOFLAVONES

Dietary sources of soy isoflavones including genistein and daidzein are reported to benefit outcomes in dietary surveys (see SOY in the Foods Library). One recent study in pre-cancerous prostate disease points to a third less well known isoflavone, equol, as being important too. Consuming moderate amounts of isoflavones in foods, around 40mg to 60mg daily, and even soy protein products , are reported as reducing risks in both cancer and any-cause disease. A supplement is a fall-back option when needed.

The majority of meta analyses, show significant reductions in both cancer incidence and recurrence – including in breast cancer. Though there have been some differing research results. For overall risk outcomes, the greatest reductions were at 20 to 40 mg/day – levels associated with >50% risk reduction in recurrence and a 20 to 40 % relative lowering of progression risk over time. Mostly, evidence from clinical trials also concludes that soy isoflavones play a role in reducing the risk of cancer recurrence and improving survival outcomes in breast cancer patients, combined with hormone therapies (see Examples)

The consensus on soy isoflavones is they show good evidence of multiple health benefits. With supplements including genistein, but not dietary sources,  a few studies have found interference with oncology drugs in breast cancer treatment. Even negative actions over time – so there is debate around these compounds. Meta-studies also state soy isoflavones could reduce thryroid function – hypothyroidism – also associated with TKI oncology drugs, something to have in mind. As always, seek qualified medical advice.

Fermented soy called natto (see Foods Library) and supplement form nattokinase have strong anti-clotting mechanisms. By reducing levels of enzymes . fibrin – that are increasingly linked to metastatic activity these are additional soy based options to consider. In prevention, population or case control meta-analysis on consumption of soy isoflavones through diet show risk reductions for most cancer types especially lung, ovarian, and gastric but also clear reductions for prostate cancers. This is reported specifically for tofu and soymilk, with no effects in other fermented or non fermented soy foods.

 

TYPICAL ABSORPTION LEVELS

1- – 10%

EXAMPLES OF IMPROVED OUTCOMES

YES
ANALYSIS

PRE-DIAGNOSIS OR PREVENTION

YES
ANALYSIS

Highlighted Studies

Soy isoflavones were associated with a 26% reduced risk of recurrence (HR = 0.74) [Hazard Ratio], particularly among postmenopausal (HR = 0.72) and estrogen receptor–positive survivors (HR = 0.82, 95% CI = 0.70 to 0.97), with the greatest risk reduction at 60 mg/day. In mortality outcomes, the reduction was mostly at 20 to 40 mg/day…An inverse association was observed for serum or plasma enterolactone, measured prediagnosis and early postdiagnosis, with cancer-spec...

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In our comprehensive evaluation of soy food consumption and breast cancer outcomes using data from a large, population-based cohort study, we found that soy food intake was inversely associated with mortality and recurrence. The inverse association did not appear to vary by menopausal status and was evident for women with ER-positive and ER-negative cancers and early and late-stage cancers… rhe hazard ratios (HRs) comparing the highest and the lowest quartiles of soy protein intake were...

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We observed a significantly lower PSA level after a 6-month challenge with a fermented soy-containing supplement, and an effect on IPSS in a subset of patients. Prescribing a fermented soy supplement in patients with an increased PCa risk could lead to a better selection of patients at real increased risk of having occult PCa [no clearly identified original tumor]

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Suggestive trends for a reduced risk of cancer recurrence were observed with increasing quintiles of daidzein and glycetin intake compared to no intake among postmenopausal women and among tamoxifen users .. Among postmenopausal women treated with tamoxifen, there was an approximately 60% reduction in breast cancer recurrence comparing the highest to the lowest daidzein intakes (>1453 micrograms (µg)/day versus < 7.7 µg/day) (HR, 0.48)  [hazard ratio]

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https://academic.oup.com/jncics/article/8/1/pkad104/74681285Soy isoflavones were associated with a 26% reduced risk of recurrence (HR = 0.74, [Hazard Ratio] , particularly among postmenopausal (HR = 0.72) and estrogen receptor–positive survivors (HR = 0.82), with the greatest risk reduction at 60 mg/day. In mortality outcomes, the reduction was mostly at 20 to 40 mg/day. Soy protein and products were inversely associated with cancer-specific mortality for estrogen receptor–positive disease (HR = 0.75)Soy isoflavones were associated with 26% reduced risk of recurrence, particularly among postmenopausal and estrogen receptor–positive survivors, with the greatest risk reduction at 60 mg/day and no further reduction at higher doses. This finding is consistent with the moderate intake of 2 to 3 servings (50-75 mg isoflavones) per day suggested as safe for women with breast cancer by the American Institute of Cancer Research (61) and the American Cancer Society (62,63). For mortality outcomes, the greatest reductions were at 20 to 40 mg/day (0.8-1.6 servings/day), which is consistent with daily intakes in Japan and Shanghai (64) but lower than current recommendations. One serving (25 mg isoflavones) can be provided by 250 mL soymilk, 85 to 100 g tofu, or 85 g cooked soybeans
https://academic.oup.com/jncics/article/8/1/pkad104/74681285Soy isoflavone intake was associated with significantly reduced risk of breast cancer recurrence for the overall population, with moderate heterogeneity (HR = 0.74, 95% CI = 0.60 to 0.92; I2 = 58.3%; P = .7 for heterogeneity). After stratifying by menopause and estrogen receptor status, the effect remained significant only for the postmenopausal (HR = 0.72, 95% CI =  0.55 to 0.94; I2 = 45.8%; P = .16 for heterogeneity) and estrogen receptor–positive (HR = 0.82, 95% CI = 0.70 to 0.97) subgroups.Dose-response analysis found evidence of nonlinearity for the association between soy isoflavones and breast cancer recurrence (P = .03 for nonlinearity), with a 30% reduction in hazard ratios at 60 mg/day but no further reduction in risk at higher intakes. Although the test for nonlinearity was not significant for soy isoflavones and breast cancer–specific mortality (P = .11 for nonlinearity) or all-cause mortality (P = .22 for nonlinearity), most of the reduction in risk was observed at the lower range of intake (20-40 mg/day)
https://jamanetwork.com/journals/jama/fullarticle/1850344.5In our comprehensive evaluation of soy food consumption and breast cancer outcomes using data from a large, population-based cohort study, we found that soy food intake was inversely associated with mortality and recurrence. The inverse association did not appear to vary by menopausal status and was evident for women with ER-positive and ER-negative cancers and early and late-stage cancers.The association of soy food intake with mortality and recurrence appears to follow a linear dose-response pattern until soy food intake reached 11 g/d of soy protein; no additional benefits on mortality and recurrence were observed with higher intakes of soy food. This study suggests that moderate soy food intake is safe and potentially beneficial for women with breast cancer.
https://www.sciencedirect.com/science/article/pii/S00904295240030054In this prospective study, we demonstrated a significant PSA modulatory effect in men with an elevated risk of PCa on a 6-month intake of a nutritional supplement with fermented soy. No significant differences on prostate volume were observed, but a significantly lower IPSS at 6 months compared to IPSS at baseline was withheld. A modulatory effect on PSA seems to influence clinical practice and the number of PCa-related investigationsDespite the fact that the median prostate volume was not statistically different after 6 months of treatment with fermented soy supplements (P = .908), we still saw an improvement in the IPSS, indicating an improvement in urinary comfort. We observed a decrease of 1 point on median IPSS from baseline compared to 6-month evaluation (P = .003). Moreover, approximately 25% of the participants (24/93) had a 3-point reduction on IPSS. An underlying explanation for this favorable effect is subject to further investigation.
https://www.sciencedirect.com/science/article/pii/S24682942210004844This prospective cohort study among 1460 early-stage BC survivors revealed that pre-diagnosis soy intake was associated with a significantly 66% reduced risk of all-cause mortality, and 64% reduced risk of BC-specific mortality during the four-year follow-up since diagnosis.Comparing with tamoxifen non-users at the lowest level of soy isoflavone intake, users of the pre-diagnosis middle intake group had a significantly reduced risk of all-cause mortality (HR 0.15 (95% CI 0.05–0.44)) and near significant reduced risk of recurrence (HR 0.57 (95% CI 0.30–1.09)). We also noted a similar pattern of post-diagnosis soy-outcome associations comparing tamoxifen users with non-users
https://bmccancer.biomedcentral.com/articles/10.1186/1471-2407-8-1324Dietary intervention with isoflavone supplementation may have biologic activity in men with biochemical recurrent prostate cancer as shown by a decline in the slope of PSA. This study may lend support to the literature that nutritional supplements have biologic activity in prostate cancer and therefore, further studies with these agents in randomized clinical trials should be encouraged.it was estimated that PSA had increased 56% per year before study entry and only increased 20% per year for the 12-month study period (p = 0.05). Specifically, the slope of PSA after study entry was significantly lower than that before study entry in 6 patients and the slope of PSA after study entry was significantly higher than before study entry in 2 patients. For the remaining 12 patients, the change in slope was statistically insignificant. Nearly two thirds of the patients were noted to have significant levels of free equol in their serum while on therapy.
https://karger.com/fok/article/23/2/75/356854/Impact-of-Soy-Foods-on-the-Development-of-Breast4However, extensive clinical and epidemiologic data show these concerns to be unfounded. Clinical trials consistently show that isoflavone intake does not adversely affect markers of breast cancer risk, including mammographic density and cell proliferation. Furthermore, prospective epidemiologic studies involving over 11,000 women from the USA and China show that postdiagnosis soy intake statistically significantly reduces recurrence and improves survival.Observational studies show that among Asian women higher soy consumption is associated with an approximate 30% reduction in risk of developing breast cancer. However, evidence suggests that for soy to reduce breast cancer risk consumption must occur early in life, that is during childhood and/or adolescence.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2394534/4it was estimated that PSA had increased 56% per year before study entry and only increased 20% per year for the 12-month study period (p = 0.05). Specifically, the slope of PSA after study entry was significantly lower than that before study entry in 6 patients and the slope of PSA after study entry was significantly higher than before study entry in 2 patients. For the remaining 12 patients, the change in slope was statistically insignificant. Nearly two thirds of the patients were noted to have significant levels of free equol in their serum while on therapy.Dietary intervention with isoflavone supplementation may have biologic activity in men with biochemical recurrent prostate cancer as shown by a decline in the slope of PSA. This study may lend support to the literature that nutritional supplements have biologic activity in prostate cancer and therefore, further studies with these agents in randomized clinical trials should be encouraged.
https://www.spmastologia.com.br/pdf/41c0a20c8ab39f51a1fc19c0d7a736de.pdf4In a meta-analysis of previously published data and ours, dietary isoflavone intake was associated with a better breast cancer prognosis. The combined HRs [Hazard Ratios] comparing the extreme categories were 0.81 for recurrence and 0.85 for all-cause mortality. A nonlinear inverse association was observed between isoflavone intake and the risk of recurrence and all-cause mortality. Our study suggests that dietary isoflavone intake is associated with a favorable prognosis in breast cancer survivorsA significantly lower risk of all-cause mortality was observed with high isoflavone intake. A meta-analysis of three studies also reported an inverse association of soy protein with mortality. Furthermore, we observed an inverse association between isoflavone intake and risk of recurrence and all-cause mortality combined in a nonlinear manner. When the meta-analysis was limited to women with ER-positive breast cancer or post-menopausal women, no adverse associations were observed
https://iv.iiarjournals.org/content/36/2/5563.5In this study, we have concluded that soy consumption and, therefore, isoflavone intake is beneficial for breast cancer prognosis and lowers breast cancer manifestation. Women with high soy and isoflavone consumption have a lower risk of being diagnosed with breast cancer when compared to women that do not have soy in their dietary plan. Initially, out of the 9,699 patients that were diagnosed with breast cancer in seven of the studies , only a quarter (25%) belonged to the high consumption group, with most belonging to the group that consumed none or up to 15 mg/day of soy and isoflavones. The odds ratio (OR) of 7.01 ....consumption of >15 mg/day is favored when compared to 0-15 mg/day.
https://www.cmaj.ca/content/182/17/18573.5High dietary intake of soy isoflavones [in asia] was associated with lower risk of recurrence among post-menopausal patients (with breast cancer positive for estrogen and progesterone receptor and those who were receiving anastrozole as endocrine therapy.Relative to post-menopausal patients in the lowest quartile of soy isoflavone intake, the risk of recurrence for post-menopausal patients in the highest quartile was significantly lower (HR = 0.67, 95% CI 0.54–0.85, p for trend = 0.02). Inverse associations were observed in patients with estrogen and progesterone receptor positive disease and those receiving anastrozole therapy.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.00892883.5In summary, our meta-analysis shows that soy isoflavone presents a protective effect for Asian pre- and post-menopausal women to some extent, but not for Western women. Further stratified and compared results (taking study design to fully consideration) gave us warnings: when we treat pooled estimates, adequate attention should be paid to study design’s influence: pooled ORs from case-control studies with lower demonstrate strength tend to suggest an inverse association between soy isoflavone intake and breast cancer risk..studies carried out in Asian countries suggested that soy isoflavone’s protective effect exist in both pre- and post-menopausal women (OR = 0.59..for premenopausal women; OR = 0.59, for postmenopausal women). However, there are some differences between the results pooled from different study designs for women in Asia... Pooled OR of studies on postmenopausal women in Western countries suggested that soy isoflavone intake has a marginally significant protective effect (OR = 0.92), but further analyses stratifying by study design found no statistically significant association.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3856358/3.5We have also observed amelioration of radiation toxicity with lycopene, another potent antioxidant agent with significant activity in prostate cancer (32,33), which lends further support to the hypothesis that certain nutritional agents such as soy isoflavones and lycopene could be added to radiation to enhance the efficacy and reduce the toxicity of radiotherapy. In summary, the results of our pilot study suggest that the adverse effects of EBRT could be ameliorated by administration of soy isoflavones in patients with prostate cancer.The results from this pilot study in locally advanced prostate cancer patients suggest that soy isoflavones taken in conjunction with EBRT may reduce the urinary, intestinal, and sexual adverse effects observed in these patients. It would take years of follow-up and a much larger number of patients to determine if the efficacy of EBRT is enhanced and the cancer relapse rate is reduced by the addition of concurrent soy isoflavones to treatment. However, PSA is a good surrogate end point for prostate cancer, and the levels of pretreatment and posttreatment PSA in this study suggest that the efficacy of the radiotherapy is not reduced by concurrent administration of soy isoflavones; if anything, the results look better in the soy arm. Patients receiving soy isoflavones during and after ERBT showed decreased incidence of urinary, gastrointestinal, and erectile dysfunction when compared to those patients receiving placeb
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8931889/3.5In this study, we have concluded that soy consumption and, therefore, isoflavone intake is beneficial for breast cancer prognosis and lowers breast cancer manifestation. Women with high soy and isoflavone consumption have a lower risk of being diagnosed with breast cancer when compared to women that do not have soy in their dietary planAccordingly, in our own statistical analysis of the data combined from these eight studies, all comparisons were of great significance and showed a favorable outcome for the group with high soy and isoflavone consumption (>15 mg/day) when compared to the low consumption group (0-15 mg/day) in all questions the authors attempted to answer via statistical analysis. Initially, out of the 9,699 patients that were diagnosed with breast cancer in seven of the studies (19-25), only a quarter (25%) belonged to the high consumption group, with most belonging to the group that consumed none or up to 15 mg/day of soy and isoflavones
https://www.mdpi.com/2072-6643/15/23/48563A possible link between diet and cancer has long been considered, with growing interest in phytochemicals. Soy isoflavones have been associated with a reduced risk of prostate cancer in Asian populations. Of the soy isoflavones, genistein and daidzein, in particular, have been studied, but recently, equol as a derivative has gained interest because it is more biologically potent. Different mechanisms of action have already been studied for the different isoflavones in multiple conditions, such as breast, gastrointestinal, and urogenital cancers. Many of these mechanisms of action could also be demonstrated in the prostate, both in vitro and in vivo. Both in vivo and in vitro preclinical data show interesting biological inhibitory influences and interactions with numerous carcinogenic and metastatic pathways. This is promising and could assign soy isoflavones a chemopreventive role in prostate cancer. However, this evidence is not yet confirmed through clinical trials, and more research is needed. Different aspects of bioavailability-influencing factors need to be taken into account in well-outlined clinical trial protocols.
https://journals.sagepub.com/doi/full/10.1177/1534735419835310#3Soy isoflavones, owing to their multiple mechanisms of effects, including the antioxidant and anti-inflammatory effects, may be used as dietary supplements to ameliorate the adverse reactions to anticancer drugs and radiation. At the same time, they may increase the efficacy of cancer chemotherapy and radiation, especially in PCa. The effect of soy isoflavones, particularly genistein, in the prevention and control of PCa has been supported by preclinical studies, meta-analyses, and clinical trialssoy supplementation may improve the efficacy and prevent the adverse effects of cancer chemotherapy and radiation therapy. Isoflavones constitute the predominant anticancer bioactive compounds in soy. Genistein, which is the most abundant and active isoflavone in soy, has a multitude of effects on cancer cells, including inhibition of NF-κB activation and DNA methylation, enhancement of histone acetylation, inhibition of cell growth and metastasis, and antiangiogenic, anti-inflammatory, and anti-oxidant effects. Isoflavones are orally bioavailable
https://molmed.biomedcentral.com/articles/10.1186/s10020-024-00778-y2.5In conclusion, our findings demonstrate that SI exerts anti-tumor effects in OS both in vitro and in vivo, positioning it as a potentially promising therapeutic agent. The therapeutic potential of SI in OS [Osteosarcoma] appears to be intricately linked with the activation of mitophagy, which is mediated via the AKT/mTOR signaling pathway.These results are similar to previous studies on genistein and daidzein mentioned above and demonstrate a positive role of SI in inhibiting OS cells in vitro. Furthermore, our in vivo experiments corroborated these findings, demonstrating that SI not only reduced tumor volume and weight but also increased the proportion of apoptotic cells while decreasing the number of active cells in OS xenografts. Our findings confirmed a promising efficiency of SI in the treatment of OS.Screenshot from 2025-06-23 21-06-51
https://foodandnutritionresearch.net/index.php/fnr/article/view/9024/152912The present study demonstrated that the genistein inhibited prostate cancer cell growth via decreasing the expression of AKR1C3 both in vitro and in vivo. The likely attendant mechanism was similar to that of the homo-AKR1C3 siRNA and the ASP-9521 AKR1C3 inhibitor. In summary, edible plant-derived compounds can be used for cancer treatment and provide new ideas for the clinical use of endocrine therapy for the treatment of CRPC. [Prostate cancer]In the present study, the growth of xenograft tumors in mice treated with genistein was inhibited, and the expression of AKR1C3 was reduced in various tissue sections of transplanted tumors. These results suggest that genistein may inhibit the proliferation of CRPC by targeting AKR1C3. The in vitro experiments also revealed that 50 μmol/L of genistein can significantly inhibit the growth of 22RV1 and VCaP cells and the expression of PSA in mRNA, as well as the protein levels.Screenshot from 2025-06-23 21-07-41

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