SOY

Tofu and soy milk can provide good levels of isoflavones genistein and daidzein (see Isoflavones in the Supplement Library). One recent study in pre-cancerous prostate disease points to a third less well known isoflavone, equol for prostate cancer. As a functional food option the well documented anti-cancer activity of soy products are most extensive in hormone driven breast and prostate cancers. There are indications in the data that both isoflavone sources in moderate doses around 40mg daily, and even soy protein products as meat substitutes can improve outcomes. Both in cancer related and any cause risk recutions.

Though not fully consistent, most meta-analyses show reduced cancer incidence and recurrence – including in breast cancer. For mortality outcomes, the greatest risk reductions were at 20 to 40 mg/day – levels associated with >50% risk reduction in recurrence and a 20 to 40 % relative improvement in overall survival 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)

In prevention, population or case control meta-analysis on consumption of soy isoflavones through diet show risk reductions for most cancer types especially colorectal, 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. There is, howver, strong evidence that the fermented soy food natto reduces vascular inflammation, but probably most would choose to use that in supplement form.

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.

Some population studies and clinical trials of metabolic health show positive effects in glucose, insulin and cholesterol levels. Overall these studies show consuming isoflavones as foods is the most beneficial way to obtain them. Results also show anti-inflammatory actions in c-reactive protein reduction. Soy proteins are generally low in sulfur-containing amino acids like cysteine and methionine, amino acids linked with cancer growth and metastasis.

EXAMPLES OF IMPROVED OUTCOMES

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PRE-DIAGNOSIS OR PREVENTION

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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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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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Among the patients with stomach cancer, frequent intake of soy food was inversely associated with the risk of all-cause (HR = 0.72, for highest vs lowest group) and stomach cancer (HR = 0.63) mortality….this prospective cohort study has clarified the associations between pretreatment intake of traditional Japanese food and the risk of death among patients with digestive tract cancers

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TABLE OF REFERENCES

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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://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://pmc.ncbi.nlm.nih.gov/articles/PMC3470874/4Suggestive 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)Of note is that we observed a possible increased risk of recurrence associated with the highest levels of daidzein and genistein intake among non-users of tamoxifen. However, this relationship was somewhat attenuated when the analyses was limited to non-users of tamoxifen who were ER– and PR− ....Perhaps for those women whose tumors have some hormone receptor positivity (a tumor is classified receptor positive if >5% of the cells express the receptor) and who do not use tamoxifen, their tumors are not benefiting from the synergistic effect of soy and tamoxifen binding to the tumor.
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.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://onlinelibrary.wiley.com/doi/10.1111/cas.144594 Among the patients with stomach cancer, frequent intake of soy food was inversely associated with the risk of all-cause (Ptrend for four frequency groups = 0.01; HR = 0.72, 95% CI: 0.50-1.04 for highest vs lowest group) and stomach cancer (Ptrend = 0.03; HR = 0.63, 95% CI: 0.40-0.99) death. A similar inverse association was also found for intake of miso soup. In contrast, frequent seaweed intake was inversely associated with the risk of all-cause death among the patients with colon cancerIn conclusion, this prospective cohort study has clarified the associations between pretreatment intake of traditional Japanese food and the risk of death among Japanese patients with digestive tract cancers. For patients with stomach cancer, intake of soy food and miso soup was inversely associated with the risk of all-cause and stomach cancer death. Among patients with colon cancer, intake of seaweed was inversely associated with the risk of all-cause death, and patients with rectal cancer who had frequently consumed seaweed tended to have a lower risk of rectal cancer death.
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://pmc.ncbi.nlm.nih.gov/articles/PMC3858084/3.5The apparent reduction in lung cancer risk associated with greater soy intake was stronger in nonsmokers than in smokers with similar level of soy protein intake (g/day). This and the non-significant association in smokers could reflect a greater degree of uncontrolled confounding in the smokers. The subjects in the nonsmokers probably differ in other factors associated with a more health-conscious lifestyle. Such factors may be difficult to separate from the measurements of soy intake. However, the soy-lung cancer associations were evaluated with the adjustment with most of other lifestyle factors among both nonsmokers and smokers in all individual studies. We observed a non-significant protective effect of soy food intake on lung cancer risk for cohort studies.In summary, the meta-analysis suggests a borderline reduction in risk of lung cancer with estimated soy protein intake in grams per day, and a significant inverse association in nonsmokers. Given the less study numbers and borderline reduction in lung cancer risk from this analysis, further updated meta-analysis is required to confirm the beneficial effect of soy food intake on lung cancer risk when new individual study available.
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.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://pmc.ncbi.nlm.nih.gov/articles/PMC11543648/3Twenty studies recorded data (1,379,632 participants) on the risk of PCA associated with total soy product consumption, with 65,909 participants newly diagnosed with PCA during the follow-up period. The analysis indicated that men who consumed soy products exhibited a significantly lower risk of PCA than those who never or rarely consumed soy products (odds ratio [OR]=0.94, 95% CI=0.91–0.97, p<0.001), with moderate heterogeneity observed (I2=40.3%). In essence, the intake of soy products demonstrated a protective effect against PCA risk. Furthermore, both cohort studies (OR=0.98, 95% CI=0.95–1.00) (I2=19.0%) and case-control studies (OR=0.94, 95% CI=0.94–0.97) (I2=40.3%) consistently concluded that soy products consumption reduces the risk of PCA in menThis meta-analysis found that soy products reduce the risk of PCA, especially localized or low-grade PCA. The frequency of consumption was negatively associated with PCA risk. Soy products can reduce the risk of PCA in African Americans and Latinos but have no impact in Japanese, Chinese and White populations. Non-fermented soy products demonstrate a reduction in PCA incidence, whereas fermented soy products do not show a significant effect. Considering the relevant limitations, large-scale prospective cohort studies are still needed to further confirm the conclusions of this study.
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.IS1
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.IS2
https://www.sciencedirect.com/science/article/abs/pii/S1043466620302982?via%3Dihub251 randomized trial were included for present study. Last analysis showed that soy product supplementation lead to significant reduction in CRP (MD −0.27 mg/L; 95% CI: −0.51, −0.02, p = 0.028) but it did not affect IL-6 (MD 0.0 pg/ml; 95% CI: −0.06, 0.06, p = 0.970) and TNF-α (MD = −0.04 pg/ml; 95% CI: −0.11, 0.03, p = 0.252). Subgroup analysis showed that soy supplementation had a significant impact on decreasing IL-6 and TNF-α levels when studies had a long-term intervention (≥12 weeks) and used low dose isoflavone (<100 mg/day).In conclusion, present systematic review and meta-analysis of all available published RCTs up to 2020 found a significant reduction in CRP levels after soy supplementation whiles IL-6 and TNF-α did not affect. Soy supplementation had a significant impact on decreasing IL-6 and TNF-α levels when studies had a long-term intervention (≥12 weeks) and used low dose isoflavone (<100 mg/day).

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