Isoflavones are naturally occurring compounds found in a wide range of plants, but among commonly consumed foods are especially abundant in soybeans and foods derived from this legume. Much of the substantial amount of research conducted on soy protein and soy foods over the past 30 y is because of their isoflavone content. Research interest in isoflavones increased dramatically beginning in the early 1990s as evidence highlighted their possible role in the prevention of a wide range of cancers, including breast, prostate, and colon cancer. Recognition that isoflavones preferentially bind to estrogen receptor (ER)β in comparison with ERα provided a conceptual basis for classifying these diphenolic molecules as selective ER modulators (SERMs). Isoflavone research soon greatly expanded beyond cancer to include areas such as coronary artery disease, bone health, cognitive function, and vasomotor symptoms of menopause. Nevertheless, safety concerns about isoflavones, based primarily on the results of rodent studies and presumed estrogenic effects, also arose. However, recent work challenges the traditional view of the estrogenicity of isoflavones. Furthermore, safety concerns have largely been refuted by intervention and population studies. On the other hand, investigation of the proposed benefits of isoflavones has produced inconsistent data. The small sample size and short duration common to many intervention trials, combined with marked interindividual differences in isoflavone metabolism, likely contribute to the conflicting findings. Also, many different intervention products have been employed, which vary not only in the total amount, but also in the relative proportion of the 3 soybean isoflavones, and the form in which they are delivered (glycoside compared with aglycone). For those interested in exploring the proposed benefits of isoflavones, studies justify an intake recommendation of ∼50 mg/d, an amount provided by ∼2 servings of traditional Asian soy foods.

Existing literatures on the potential impact of soy protein consumption on kidney function present conflicting findings. In this study, a meta-analysis has been conducted to assess the impact of soy protein consumption in comparison to animal protein consumption among individuals with chronic kidney disease (CKD).

A structured electronic search was conducted on Medline, EMBASE, and Cochrane Library for randomized controlled trials published up to March 2024. The outcome measures were serum creatinine (SCR), triglyceride (TG), total cholesterol (TC), calcium (Ca), C-reactive protein, proteinuria, high-density lipoprotein (HDL), low-density lipoprotein (LDL), uric acid (UA) and phosphorus concentrations. Mean differences were calculated for net changes using random-effects models.

Eighteen trials with a total of 522 participants were included in this systematic review. The results showed that consumption of soy protein led to a significant decrease in total cholesterol, LDL, and proteinuria levels. The average reduction was  - 20.55 mg/dL (95% CI  - 38.25,  - 2.85 mg/dL) for total cholesterol (P = 0.02),  - 8.26 mg/dL (95% CI  - 13.35,  - 3.17 mg/dL; P = 0.001) for LDL and  - 140.53 (95% CI  - 205.83,  - 75.23 mg/day) for proteinuria. No statistically significant impact was observed on serum creatinine, triglycerides, calcium, C-reactive protein, HDL, uric acid, or phosphorus levels.

The findings of the meta-analysis showed a potential protective impact of soy protein intake on hyperlipidemia and proteinuria in CKD patients. It is important to note that the evidence presented may be of limited accuracy due to relatively small number of trials and participants.

Cancer is a significant cause of death worldwide. It has been suggested that the consumption of flavonoids decreases the risk for cancer by increasing phase II enzymes, such as Nicotinamide Adenine Dinucleotide Phosphate Hydrogen (NAD(P)H) quinone oxidoreductase 1 (NQO1), glutathione S-transferases, and Uridine 5'-diphospho- (UDP)-glucuronosyltransferases that assist in removing carcinogens from the human body. Flavonoids are bioactive compounds found in a variety of dietary sources, including fruits, vegetables, legumes, nuts, and teas. As such, it is important to investigate which flavonoids are involved in the metabolism of carcinogens to help reduce the risk of cancer. Therefore, the objective of this narrative review was to investigate the effects of commonly consumed flavonoids on NQO1 mRNA expression, protein, and activity in human cell and murine models. PubMed was used to search for peer-reviewed journal articles, which demonstrated that selected flavonoids (e.g., quercetin, apigenin, luteolin, genistein, and daidzein) increase NQO1, and therefore, increase the excretion of carcinogens. However, more research is needed regarding the mechanisms by which flavonoids induce NQO1. Furthermore, it is suggested that future efforts focus on providing precise flavonoid recommendations to decrease the risk factors for chronic diseases.

This study aimed to clarify the associations between isoflavone intake and the volume changes of brain regions, specifically the hippocampus and total grey matter (TGM), over 10 years in Japanese middle-aged and older community dwellers.

Data from the National Institute for Longevity Sciences-Longitudinal Study of Aging of 654 men and 671 women aged 40-85 years at baseline (6th wave survey, 2008-2010) who participated in the follow-up study (9th wave survey, 2018-2022) were analyzed. Total isoflavone intake was estimated based on a 3-day dietary record and categorized into quintile groups. The volumes of the hippocampus and TGM were measured by T1-weighted magnetic resonance imaging and longitudinal FreeSurfer software. Estimated mean brain volume changes by quintile of total isoflavone intake were assessed by a general linear model, with a stratified analysis by age group (< 65/≥65 years).

There were no significant associations between quintile of isoflavone intake and both brain volume changes over 10 years in all participants. On stratification by age group, the multivariable-adjusted difference over time and % change in hippocampal volume were more strongly associated with quintile of total isoflavone intake in those aged ≥ 65 years (difference over time: p for trend = 0.009; % change: p for trend = 0.012). There were no significant longitudinal associations between quintile of total isoflavone intake and TGM volume change in both age groups.

In older Japanese people aged ≥ 65 years, increased intake of total isoflavones might be a new nutritional strategy to prevent hippocampal atrophy.

This narrative review aims to determine the impact of postdiagnosis isoflavone intake, via supplements and foods, on breast cancer outcomes. Foods derived from soybeans are uniquely rich sources of isoflavones, naturally occurring compounds that can bind to estrogen receptors although the extent to which they exert estrogen-like effects in humans is unclear. Isoflavones have been rigorously investigated for a wide range of health benefits including breast cancer prevention. However, their classification as phytoestrogens has led to concern that isoflavones and hence, soy food consumption, could worsen the prognosis of women with breast cancer and interfere with the efficacy of endocrine therapy for this disease.

Research in athymic ovariectomized mice shows isoflavones stimulate the growth of existing estrogen-sensitive mammary tumors. However, extensive clinical research indicates that neither soy foods nor isolated isoflavones affect markers of breast cancer risk including mammographic density and breast cell proliferation. No effects are observed even when isoflavone exposure greatly exceeds typical intake in Asian countries. Furthermore, the results from epidemiologic studies indicate postdiagnosis isoflavone intake from soy foods reduces recurrence and possibly mortality from breast cancer. Additionally, the limited observational data do not show that isoflavones interfere with the efficacy of tamoxifen or aromatase inhibitors. Regardless of their treatment status, evidence indicates that women with breast cancer can safely consume soy foods. Limiting intake to no more than two servings of traditional Asian soy foods daily, an amount that provides approximately 50 mg isoflavones, is recommended, not because data indicate exceeding this amount is harmful, but because few population-based studies involved participants consuming more than this intake recommendation.

Background/Objectives: Isoflavone (ISO) may have immunosuppressive and promoting effects. In this study, we aimed to examine the association between maternal dietary ISO intake during pregnancy and childhood allergic rhinoconjunctivitis at the age of 3 years using the Japanese Birth Cohort data. Methods: Overall, 78,549 mother-child pairs were studied. Maternal dietary ISO intake (the sum of genistein and daidzein) during pregnancy was evaluated using a food frequency questionnaire. Information on physician-diagnosed allergic rhinoconjunctivitis was collected from the caregiver-reported questionnaire. After classifying ISO intake into quartiles (Q1: reference), multivariable logistic regression analysis was employed to explore the association with allergic rhinoconjunctivitis. Results: No association was observed between maternal ISO intake and allergic rhinoconjunctivitis in any child. However, in the sex-stratified analysis, maternal ISO intake linked to allergic rhinoconjunctivitis in female children positively (Q2, adjusted odds ratio [aOR]: 1.22, 95% confidence interval [CI]: 1.06-1.40; Q3, aOR: 1.17, 95% CI: 1.01-1.35; Q4, aOR: 1.24, 95% CI: 1.07-1.44). Conclusions: Maternal dietary ISO intake during pregnancy was sex-specifically linked to childhood allergic rhinoconjunctivitis in children. These findings provide insights into the need for estimating the optimal ISO consumption during pregnancy for allergy avoidance in children.

Although phytoestrogens modulated pancreatic tumour growth in experimental studies, it remains unclear whether phytoestrogen intake is associated with pancreatic cancer.

Of 92,278 persons who completed the Diet History Questionnaire in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, 346 were diagnosed with pancreatic cancer within a median follow-up of 9.4 years. Cox proportional hazards regression was used to evaluate pancreatic cancer risk in relation to phytoestrogen intake.

After adjustment for confounders, intakes of glycitein and formononetin were associated with a reduced risk of pancreatic cancer [highest vs. lowest quartile, hazard ratio (HR) (95% confidence interval (CI)) for glycitein: 0.60 (0.39, 0.92); P for linear trend: 0.01; HR for formononetin: 0.51 (0.37, 0.70); P for linear trend: 0.005]. These associations were stronger and their linear trends across the quartiles of intakes were more statistically significant among ever smokers than never-smokers. A reduced risk was also observed for ever smokers in the highest quartile of total isoflavones or daidzein compared with those in the lowest quartile.

Our study suggests that high intakes of total isoflavones and some individual isoflavones were inversely associated with pancreatic cancer risk, but this potential protective effect was confined to ever smokers.

Isoflavones are estrogen-like compounds found in plants and their health effects remain equivocal. We investigated dietary isoflavone intake and its associated factors in Korean breast cancer survivors, with a comparison to cancer-free women.

The usual dietary intake of breast cancer survivors (n = 981, mean age 52 yrs) in 9 hospitals between 2012 and 2019 was assessed using 3-day food records or food frequency questionnaires (FFQs). They were age-matched to 2,943 cancer-free women who completed FFQs as part of a nationwide study conducted between 2012 and 2016. We used the flavonoid database of common Korean foods and the Phenol-Explorer database to estimate isoflavone intake. The contribution of each food or food group to the total isoflavone intake was calculated. The adjusted least-squares means of dietary isoflavone intake according to lifestyle and clinical factors were calculated using generalized linear models.

Breast cancer survivors had a higher mean dietary isoflavone intake (23.59 mg/day) than cancer-free women (17.81 mg/day). Major food sources, including tofu, soybeans, and doenjang, contributed to over 70% of the isoflavone intake in both groups. When we estimated dietary isoflavone intake according to lifestyle characteristics, isoflavone intake increased with higher scores of adherence to the American Cancer Society dietary guidelines but decreased with increasing body mass index in both groups. Among cancer-free women, dietary isoflavone intake was higher among those who had never smoked and among dietary supplement users. Among breast cancer survivors, dietary isoflavone intakes did not vary with clinical characteristics, including time since surgery and estrogen receptor status.

Breast cancer survivors were more likely to consume isoflavones than age-matched cancer-free women. Dietary isoflavone intake was associated with healthy lifestyle characteristics in women both with and without breast cancer. Further research is needed to understand the role of the higher isoflavone intake among breast cancer survivors compared to cancer-free women on their prognosis.

Despite recommendations to increase plant food consumption for public and planetary health and the role that soy foods can play in plant-predominant diets, controversies around the effects of soy foods, especially soy isoflavones, are a barrier to their intake. Given their cardioprotective effects and ability to alleviate menopausal symptoms, addressing these concerns is particularly relevant to women. This systematic review and meta-analysis of randomized controlled trials aimed to determine the effect of soy isoflavones on measures of estrogenicity in postmenopausal women. MEDLINE, Embase, and Cochrane Library were searched through August 2024 for randomized trials ≥3-mo investigating soy isoflavones compared with non-isoflavone controls in postmenopausal women. Outcomes included endometrial thickness (ET), vaginal maturation index (VMI), follicle-stimulating hormone (FSH), and estradiol. Independent authors extracted data and assessed risk of bias. Grading of Recommendations, Assessment, Development and Evaluation was used to assess certainty of evidence. We included 40 trials (52 trial comparisons, n = 3285) assessing the effect of a median reported dose of 75 mg/d of soy isoflavones in substitution for non-isoflavone controls over a median of 24 wk. Soy isoflavones had no statistically significant effect on any measure of estrogenicity; ET [mean difference, -0.22 mm (95% confidence interval, -0.45, 0.01 mm), PMD = 0.059], VMI [2.31 (-2.14, 6.75), PMD = 0.310], FSH [-0.02 IU/L (-2.39, 2.35 IU/L), PMD = 0.987], and estradiol [1.61 pmol/L (-1.17, 4.38 pmol/L), PMD = 0.256]. The certainty of evidence was high to moderate for all outcomes. Current evidence suggests that soy isoflavones do not exhibit estrogenic effects compared with non-isoflavone controls on 4 measures of estrogenicity in postmenopausal women. This synthesis supports that soy isoflavones likely act as selective estrogen receptor modulators, differing clinically from the hormone estrogen. Addressing public health concerns may promote soy foods as high-quality plant protein sources with low environmental impact and cost, particularly benefiting postmenopausal women and aligning with sustainable dietary patterns and guidelines. This study was registered in PROSPERO as CRD42023439239.

The overall understanding of the correlations between mortality risk and phytoestrogens in general population remains limited. We examined the association between urinary phytoestrogen levels and all-cause and cardiovascular mortality based on the National Health and Nutrition Examination Survey (NHANES).

Weighted Cox proportional hazard regression models were employed to calculate adjusted hazard ratios (HRs) and their 95% confidence intervals (CIs). Nonlinear relationships were assessed using multivariable-adjusted restricted cubic splines (RCS).

In the fully adjusted model, the highest quartiles of urinary genistein levels were correlated with significantly elevated all-cause (HR = 1.36, 95%CI: 1.16-1.59) and cardiovascular (HR = 1.58, 95%CI: 1.20-2.09) mortality. Urinary enterolactone levels in the third quartile were associated with reduced all-cause (HR = 0.77, 95%CI: 0.65-0.90) and cardiovascular (HR = 0.74, 95%CI: 0.55-0.99) mortality. In the highest quartiles of urinary daidzein levels, the cardiovascular mortality was significantly increased (HR = 1.44, 95%CI: 1.09-1.90). RCS showed an non-linear relationship between urinary daidzein levels and all-cause mortality (P = 0.04).

In the context of a nationally representative sample, genistein exhibited associations with elevated all-cause and cardiovascular mortality, whereas enterolactone showed an association with reduced mortality. The dose-response relationship between urinary daidzein levels and all-cause mortality as well as sex-specific disparities in the impact of phytoestrogen levels should be considered.

Dietary isoflavones have been associated with a lower risk of gastric cancer (GC), but the evidence for this association is still limited. We investigated the association between isoflavone intake and GC risk using data from a case-control study including 230 incident, histologically confirmed GC cases and 547 controls with acute, non-neoplastic conditions. Dietary information was collected through a validated food frequency questionnaire (FFQ) and isoflavone intake was estimated using ad hoc databases. We estimated the odds ratios (OR) and the corresponding 95% confidence intervals (CI) of GC using logistic regression models, including terms for total energy intake and other major confounders. The OR for the highest versus the lowest tertile of intake was 0.65 (95%CI = 0.44-0.97, p for trend = 0.04) for daidzein, 0.75 (95%CI = 0.54-1.11, p for trend = 0.15) for genistein, and 0.66 (95%CI = 0.45-0.99, p for trend = 0.05) for total isoflavones. Stratified analyses by sex, age, education, and smoking showed no heterogeneity. These findings indicate a favorable effect of dietary isoflavones on GC.

Over the past decades, there has been a significant increase in the burden of neurological diseases, including neurodegenerative disorders, on a global scale. This is linked to a widespread demographic trend in which developed societies are aging, leading to an increased proportion of elderly individuals and, concurrently, an increase in the number of those afflicted, posing one of the main public health challenges for the coming decades. The complex pathomechanisms of neurodegenerative diseases and resulting varied symptoms, which differ depending on the disease, environment, and lifestyle of the patients, make searching for therapies for this group of disorders a formidable challenge. Currently, most neurodegenerative diseases are considered incurable. An important aspect in the fight against and prevention of neurodegenerative diseases may be broadly understood lifestyle choices, and more specifically, what we will focus on in this review, a diet. One proposal that may help in the fight against the spread of neurodegenerative diseases is a diet rich in flavonoids. Flavonoids are compounds widely found in products considered healthy, such as fruits, vegetables, and herbs. Many studies indicated not only the neuroprotective effects of these compounds but also their ability to reverse changes occurring during the progression of diseases such as Alzheimer's, Parkinson's and amyotrophic lateral sclerosis. Here, we present the main groups of flavonoids, discussing their characteristics and mechanisms of action. The most widely described mechanisms point to neuroprotective functions due to strong antioxidant and anti-inflammatory effects, accompanied with their ability to penetrate the blood-brain barrier, as well as the ability to inhibit the formation of protein aggregates. The latter feature, together with promoting removal of the aggregates is especially important in neurodegenerative diseases. We discuss a therapeutic potential of selected flavonoids in the fight against neurodegenerative diseases, based on in vitro studies, and their impact when included in the diet of animals (laboratory research) and humans (population studies). Thus, this review summarizes flavonoids' actions and impacts on neurodegenerative diseases. Therapeutic use of these compounds in the future is potentially possible but depends on overcoming key challenges such as low bioavailability, determining the therapeutic dose, and defining what a flavonoid-rich diet is and determining its potential negative effects. This review also suggests further research directions to address these challenges.

Isoflavones are naturally occurring plant compounds found in uniquely high amounts in soybeans and foods made from this legume. These soybean constituents have been proposed to exert several health benefits and as such they have been the subject of an enormous amount of research. This research includes randomized controlled trials (RCTs) and epidemiologic investigations. Although statistically significant associations between isoflavone intake and a wide range of health outcomes have been identified in cohorts involving low-isoflavone intake populations, we suggest that these associations are unlikely to have a causal basis because exposure is too low for isoflavones to exert physiologic effects. In cohorts involving predominantly non-Asian, non-vegetarian populations, the highest isoflavone intake category is typically ≤3 mg/d, an amount of isoflavones provided by ∼30 mL (2 tablespoons) of soymilk made from whole soybeans. In comparison, mean isoflavone intake in the upper intake categories in observational studies involving high-isoflavone intake populations is typically ≥50 mg/d. In RCTs, intervention doses of isoflavones typically range between 40 and 100 mg/d. Health professionals advising patients and clients about soy food and isoflavone intake need to be aware of the limitations of epidemiologic research involving low-isoflavone intake populations. Intake recommendations are best based on the results of RCTs using clinically relevant doses of isoflavones and epidemiologic studies involving populations for whom soy foods are a habitual part of the diet.

The association between soy product consumption and cancer risk varies among studies. Therefore, this comprehensive meta-analysis of observational studies examines the association between soy product consumption and total cancer risk.

This study was conducted following the PRISMA guidelines. Up to October 2023, all eligible published studies were searched through PubMed and Web of Science databases.

A total of 52 studies on soy product consumption were included in this meta-analysis (17 cohort studies and 35 case-control studies). High consumption of total soy products (RR: 0.69; 95% CI: 0.60, 0.80), tofu (RR: 0.78; 95% CI: 0.70, 0.86), and soymilk (RR: 0.75; 95% CI: 0.60, 0.93) were associated with reduced total cancer risk. No association was found between high consumption of fermented soy products (RR: 1.18; 95% CI: 0.95, 1.47), non-fermented soy products (RR: 0.95; 95% CI: 0.77, 1.18), soy paste (RR: 1.00; 95% CI: 0.88, 1.14), miso soup (RR: 0.99; 95% CI: 0.87, 1.12), or natto (RR: 0.96; 95% CI: 0.82, 1.11) and cancer risk. A 54 g per day increment of total soy products reduced cancer risk by 11%, a 61 g per day increment of tofu reduced cancer risk by 12%, and a 23 g per day increment of soymilk reduced cancer risk by 28%, while none of the other soy products were associated with cancer risk.

Our findings suggest that high total soy product consumption, especially soymilk and tofu, is associated with lower cancer risk. More prospective cohort studies are still needed to confirm the causal relationship between soy product consumption and cancer risk.

Diets rich in minimally processed plant-based foods are recommended to breast cancer patients, and some may have an interest in whole-food, plant-based (WFPB) diets that avoid animal-based foods, added fats, and refined sugars. Within WFPB diets, the intakes of isoflavones, omega-6 polyunsaturated fatty acids (n-6 PUFAs), and omega-3 polyunsaturated FAs (n-3 PUFAs), which have been discussed in reference to breast cancer outcomes, have not been well characterized.

Women with stage IV breast cancer on stable therapy were randomized 2:1 into (1) a WFPB intervention (N = 21) or (2) usual care (N = 11) for 8 weeks. Three meals per day were provided. Outcomes presented here include dietary intake of isoflavones, n-3 and n-6- PUFAs, which were assessed using three-day food records at baseline and 8 weeks. Baseline and 8-week mean intake within groups were compared using the Wilcoxon signed-rank test and between control and intervention groups by a two-sample t-test.

The WFPB intervention participants increased their daily consumption of total isoflavones from a mean of 0.8 mg/day to 14.5 mg/day (p < 0.0001) and decreased the n-6:n-3 ratio of their diet from a mean of 9.3 to 3.7 (p < 0.0001). Within the WFPB group, linoleic acid (n-6 PUFA) consumption decreased by a mean of 3.8 g (p = 0.0095), from 12.8 g/day to 9.0 g/day; total n-3 PUFA consumption increased by a mean of 1.1 g (p = 0.0005), from 1.6 g/day to 2.7 g/day.

Transitioning to a WFPB diet resulted in significantly increased isoflavone intake and decreased n-6:n-3 ratio in women with breast cancer.

Phytonutrient intakes may improve outcomes following breast cancer, but the impact of postdiagnosis introduction vs established prediagnostic exposure as well as optimum doses has not been established. Evidence from observational studies for key exposures was evaluated, including dosage and intake time frames.

MEDLINE, EMBASE, CINAHL, Cochrane Library, ClinicalTrials.gov, and the ISRCTN registry were searched for prospective and retrospective observational studies investigating the impact of soybean, lignans, cruciferous (cabbage-family) vegetables, green tea, or their phytonutrients on breast cancer survival outcomes. A random-effects model was used to calculate summary hazard ratios (HRs) and 95% confidence intervals (CIs). Nonlinear dose-response analyses were conducted using restricted cubic splines.

Thirty-two articles were included. Soy isoflavones were associated with a 26% reduced risk of recurrence (HR = 0.74, 95% CI = 0.60 to 0.92), particularly among postmenopausal (HR = 0.72, 95% CI = 0.55 to 0.94) 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. Soy protein and products were inversely associated with cancer-specific mortality for estrogen receptor-positive disease (HR = 0.75, 95% CI = 0.60 to 0.92). An inverse association was observed for serum or plasma enterolactone, measured prediagnosis and early postdiagnosis, with cancer-specific mortality (HR = 0.72, 95% CI = 0.58 to 0.90) and all-cause mortality (HR = 0.69, 95% CI = 0.57 to 0.83). No effects were observed for cruciferous vegetables. There was a 44% reduced risk of recurrence with prediagnostic green tea for stage I and II breast cancer (HR = 0.56, 95% CI = 0.38 to 0.83).

Soy, enterolactone, and green tea demonstrated significant risk reductions in outcomes following breast cancer. Evidence is needed regarding the impact of postdiagnostic introduction or substantial increase of these exposures.

Soybean (Glycine max) is an important ingredient of cuisines worldwide. While there is a wealth of evidence that soybean could be a good source of macronutrients and phytochemicals with health-promoting effects, concerns regarding adverse effects have been raised. In this work, we reviewed the current clinical evidence focusing on the benefits and risks of soybean ingredients. In breast, prostate, colorectal, ovarian, and lung cancer, epidemiological studies showed an inverse association between soybean food intake and cancer risks. Soybean intake was inversely correlated with risks of type 2 diabetes mellitus (T2DM), and soy isoflavones ameliorated osteoporosis and hot flashes. Notably, soybean was one of the dietary protein sources that may reduce the risk of breast cancer and T2DM. However, soybean had adverse effects on certain types of drug treatment and caused allergies. In sum, this work provides useful considerations for planning clinical soybean research and selecting dietary protein sources for human health.

Genistein is a natural compound belonging to flavonoids, having antioxidant, anti-inflammatory, and anti-neoplastic properties. Genistein is considered a phytoestrogen. As such, genistein can bind estrogen receptors (ERα and ERβ), although with a lower affinity than that of estradiol. Despite considerable work, the effects of genistein are not well established yet. This review aims to clarify the role of genistein on female and male reproductive functions in mammals. In females, at a high dose, genistein diminishes the ovarian activity regulating several pathway molecules, such as topoisomerase isoform I and II, protein tyrosine kinases (v-src, Mek-4, ABL, PKC, Syk, EGFR, FGFR), ABC, CFTR, Glut1, Glut4, 5α-reductase, PPAR-γ, mitogen-activated protein kinase A, protein histidine kinase, and recently circulating RNA-miRNA. The effect of genistein on pregnancy is still controversial. In males, genistein exerts an estrogenic effect by inducing testosterone biosynthesis. The interaction of genistein with both natural and synthetic endocrine disruptors has a negative effect on testis function. The positive effect of genistein on sperm quality is still in debate. In conclusion, genistein has a potentially beneficial effect on the mechanisms regulating the reproduction of females and males. However, this is dependent on the dose, the species, the route, and the time of administration.

Soy drinks are an increasingly consumed option within the Western diet. However, there are concerns about potential endocrine disruptor effects and possible impact on women's reproductive health. This review evaluates scientific documents in gynecology and obstetrics under an evidence-based medicine approach. All methods adhered to PRISMA 2020 declaration guidelines. The evaluated studies do not support a positive association between soy intake and early puberty or breast cancer; instead, a protective effect against such neoplasm was observed. Transplacental passage of soy isoflavones and their presence in breast milk has been reported without any maternal-fetal complications nor congenital malformations. Exposure to soy-derived products appears to have a neutral effect on body weight and bone health. Studies performed in adults indicate that soy may promote a minimal increase in thyrotropin (TSH) in subjects with subclinical hypothyroidism. The impact of soy-based foods on gut microbiota appears favorable, especially when consuming fermented products. Many of the human studies have been conducted with isoflavones supplements, isolated or textured soy proteins. Therefore, the results and conclusions should be interpreted cautiously, as these are not entirely applicable to commercial soy beverages.

Phytoestrogens, such as isoflavones, are bioactive compounds found in plants with defense and protection functions. In the human body, they simulate the behavior of the hormone estradiol and can modulate the function of the male hypothalamic-pituitary-gonadal axis. This study aims to describe the effects of genistein on sperm quality of Wistar rats (male/adult) after a short oral administration protocol (50 mg/day, for 5 days), focusing on mitochondrial function. No signs of toxicity were observed in the animals during the period. The testicular mass of rats from the genistein-treated group was lower than that from the control group. Isoflavone increased the number of viable Leydig and Sertoli cells, spermatogonia, and primary spermatocytes in the treated group. The rounded spermatid count was similar to the control group, and a decrease in elongated spermatids was observed in the treated group. Genistein treatment increased plasma testosterone levels in the treated group. To the best of our knowledge, this is the first report of an in vivo short protocol demonstrating that genistein administration stimulates the overall oxygen consumption in rat seminal samples. Therefore, genistein induced a pro-spermatogenesis effect, enhanced plasma testosterone levels, and increased oxygen consumption, improving sperm mitochondrial efficiency. Similar protocols can be explored in animal and human infertility issues.

Maintaining muscle mass, strength, and function is crucial for our aging population. Exercise and dietary protein intake are recommended strategies; however, animal proteins have been the most studied. Plant-based protein sources have lower digestibility and incomplete amino acid profiles. However new innovative plant-based proteins and products may have overcome these issues. Therefore, this systematic review aimed to synthesize the current research and evaluate the effects of plant-based protein interventions compared to placebo on body composition, strength, and physical function in older adults (≥60 years old). The secondary aim was whether exercise improved the effectiveness of plant-based protein on these outcomes. Randomized controlled trials up to January 2023 were identified through Medline, EMBASE, CINAHL, and Cochrane Library databases. Studies contained a plant-protein intervention, and assessed body composition, strength, and/or physical function. Thirteen articles were included, all using soy protein (0.6-60 g daily), from 12 weeks to 1 year. Narrative summary reported positive effects on muscle mass over time, with no significant differences compared to controls (no intervention, exercise only, animal protein, or exercise + animal protein interventions). There was limited impact on strength and function. Meta-analysis showed that plant-protein interventions were comparable to controls, in all outcomes. In conclusion, plant-protein interventions improved muscle mass over time, and were comparable to other interventions, warranting further investigation as an anabolic stimulus in this vulnerable population.

There is a longstanding interest in the relationship between diet and hot flash symptoms during midlife, especially in whether phytoestrogens ease menopausal symptoms. The purpose of this study was to examine hot flashes, night sweats, trouble sleeping, and vaginal dryness in relation to the intake of foods rich in phytoestrogens among Bangladeshi women aged 35 to 59 years who were living either in Sylhet, Bangladesh (n = 157) or as migrants in London (n = 174). Consumption ranges for phytoestrogens were constructed from food frequencies. We hypothesized that diets rich in isoflavones, lignans, and coumestrol would be associated with lower symptom frequencies. However, adjusted logistic regression results showed that with each incremental increase in general phytoestrogen consumption (scale of 0 to 10), the likelihood of hot flashes increased by 1.4%. Each incremental increase in lignan consumption raised the likelihood of hot flashes by 1.6%. In contrast, the odds of vaginal dryness decreased by 2%, with each incremental increase in phytoestrogen and lignan consumption, and by 4%, with each incremental increase in isoflavone consumption. Night sweats and trouble sleeping were not associated with phytoestrogen intake in logistic regressions. Our findings add to the conflicting data on relationships between phytoestrogens and symptoms associated with menopause.

Epidemiological studies that focus on the relationship between dietary isoflavone intake and the risk of breast cancer still lead to inconsistent conclusions. Herein, we conducted a meta-analysis of the latest studies to explore this issue.

We performed a systematic search using Web of Science, PubMed, and Embase from inception to August 2021. The robust error meta-regression (REMR) model and generalized least squares trend (GLST) model were used to establish dose-response relationships between isoflavones and breast cancer risk.

Seven cohort studies and 17 case-control studies were included in the meta-analysis, and the summary OR for breast cancer was 0.71 (95% CI 0.72-0.81) when comparing the highest to the lowest isoflavone intake. A subgroup analysis further showed that neither menopausal status nor ER status has a significant influence on the association between isoflavone intake and breast cancer risk, while the isoflavone intake doses and study design does. When the isoflavones exposure was less than 10 mg/day, no effects on breast cancer risk were detected. The inverse association was significant in the case-control studies but not in the cohort studies. In the dose-response meta-analysis of the cohort studies, we observed an inverse association between isoflavone intake and breast cancer: a 10 mg/day increase in isoflavone intake was related to reductions of 6.8% (OR = 0.932, 95% CI 0.90-0.96) and 3.2% (OR = 0.968, 95% CI 0.94-0.99) in breast cancer risk when using REMR and GLST, respectively. In the dose-response meta-analysis of the case-control studies, the inverse association for every 10 mg/day isoflavone intake was associated with breast cancer risk reductions by 11.7%.

present evidence demonstrated that taking in dietary isoflavone is helpful in reducing the breast cancer risk.

Human milk (HM) is a complex biological system that contains a wide range of bioactive components including oestrogens and progesterone. Whilst maternal oestrogens and progesterone concentrations drop rapidly after birth, they remain detectable in HM across lactation. Phytoestrogens and mycoestrogens, which are produced by plants and fungi, are also present in HM and can interact with oestrogen receptors to interfere with normal hormone functions. Despite the potential impact of HM oestrogens and progesterone on the infant, limited research has addressed their impact on the growth and health of breastfed infants. Furthermore, it is important to comprehensively understand the factors that contribute to these hormone levels in HM, in order to establish effective intervention strategies. In this review, we have summarized the concentrations of naturally occurring oestrogens and progesterone in HM from both endogenous and exogenous sources and discussed both maternal factors impacting HM levels and relationships with infant growth.

Dairy and nondairy plant-based alternative proteins are reported to differentially influence body weight; however, most research has compared plant-based alternatives with isolated dairy proteins rather than a complete milk protein (containing casein and whey). This is notable given that people do not generally consume isolated dairy proteins. Therefore, the present study aimed to investigate the impact of a soy protein isolate (SPI) on factors influencing body weight gain in male and female mice in comparison to skim milk powder (SMP). Based on current knowledge in rodents, we hypothesized that SPI would promote body weight gain compared with SMP. Mice (n = 8 per sex per diet) consumed a moderate-fat diet (35% kcal from fat) containing either SPI or SMP for 8 weeks. Body weight and food intake were measured weekly. Energy expenditure, physical activity, and substrate use were measured using metabolic cages. Fecal energy content was measured with bomb calorimetry. Body weight gain and food intake during the 8-week feeding study was not different in mice consuming either SPI or SMP; however, males had a higher body weight, adiposity, and feed efficiency compared with females (all P < .05). Fecal energy content was approximately 7% higher in both male and female mice fed the SPI diet compared with the SMP diet. Neither protein source affected substrate utilization, physical activity, or energy expenditure. Physical activity in the dark phase trended higher in females compared with males (P = .0732). The present study suggests that the consumption of SPI in the context of a moderate-fat diet has little impact on numerous factors influencing body weight regulation in male and female mice compared with a complete milk protein.

Population-level nutritional assessments often rely on self-reported data, which increases the risk of recall bias. Here, we demonstrate that wastewater-based epidemiology can be used for near real-time population dietary assessments. Neighbourhood-level, untreated wastewater samples were collected monthly from within an urban population in the south-western United States from August 2017 to July 2019. Using liquid chromatography-tandem mass spectrometry, we identify recurring seasonal dynamics in phytoestrogen consumption, including dietary changes linked to the winter holiday season. Using 16S ribosomal RNA gene amplicon sequencing, we demonstrated the feasibility of detecting sewage-derived human gut bacterial taxa involved in phytoestrogen metabolism, including Bifidobacterium, Blautia and Romboutsia. Combined metabolomic and genomic wastewater analysis can inform nutritional assessments at population scale, indicating wastewater-based epidemiology as a promising tool for actionable and cost-effective data collection to support public health nutrition.

We evaluated the association between total soy, soy product (natto, miso and tofu) and isoflavone intake and incident disabling dementia in a Japanese population.

We conducted a population-based prospective study in 18,991 men and 22,456 women. Intake of soy products and isoflavone was calculated using a validated food frequency questionnaire when participants were 45-74 years old (1995 and 1998). Incident disabling dementia was defined by the daily living disability status related to dementia in the long-term care insurance program of Japan from 2006 to 2016. Multivariate hazard ratios (HRs) and 95% confidence intervals (CIs) of disabling dementia were calculated by quintiles of total soy, individual soy product and isoflavone intake, using Cox proportional hazard regression models.

Total soy product intake was not associated with disabling dementia risk in both men and women. By individual soy products, natto intake was marginally inversely associated with disabling dementia in women (trend P = 0.050). When we stratified by age, this inverse association was clearer in women aged under 60 years (multivariate HR for the highest versus lowest quintile was 0.78, 95% CI 0.59-1.04, trend P = 0.020 for those aged under 60 years and 0.90, 95% CI 0.77-1.05, trend P = 0.23 for those aged 60 years and older, respectively). Any soy product or isoflavone intake was not associated with disabling dementia risk in men.

Although total soy product intake was not associated with disabling dementia risk, natto intake may contribute to reducing the risk of disabling dementia in women, especially in those aged under 60 years.

Soybean meal (SBM) is a co-product of the soybean oil industry that is rich in bioactive compounds, such as isoflavones. We aimed to study the effects of processing SBM by fermentation (Saccharomyces cerevisiae) (FSBM) and enzymatic hydrolysis (CelluMax C, a commercial cellulase) (ESBM) on its chemical composition, with emphasis on isoflavones. Fermentation increased protein content by 9%, ash content by 7%, dietary fiber by 11% and minerals by up to 38%, except for iron, which decreased by 26%. Fermentation completely removed oligosaccharides from SBM, while enzymatic processing decreased oligosaccharides by 45% in SBM. Both processes converted glycosylated isoflavones into the corresponding aglycones, the content of which increased by up to 7.7-fold. Biscuits containing SBM, FSBM and ESBM could be labeled as dietary sources of dietary fibers, potassium, phosphorous, calcium and zinc, as well as high in proteins, copper, iron, manganese and magnesium. While FSBM biscuits had lower sensory scores compared to SBM biscuits, ESBM biscuits had equivalent scores. During storage for 180 days at room temperature, the isoflavone profile of all biscuits remained stable. Moreover, storage did not impair microbiological and sensory qualities of any biscuits. Altogether, ESBM biscuits show great marketing potential.

This study compared dietary isoflavone aglycones with the glycoside conjugates in a novel model of postmenopausal status, the aging domestic hen (Gallus gallus domesticus), to determine the effects on reproductive performance, cholesterol levels, and nutritional quality of eggs laid. Hens, 18 mo old, were randomized into four groups (n = 10/group) and fed for 28 d a conventional poultry corn/soymeal diet (Control), or diets supplemented with isoflavone glycosides from soy germ (diet A), isoflavone aglycons from a soy germ pasta (diet B), or conventional pasta lacking isoflavones (diet C). The egg-laying rate was recorded daily, plasma isoflavones and cholesterol were measured, and the nutritional composition of the eggs was determined. Egg-laying declined over a 4-week period in hens in the Control group and those fed isoflavone glycosides (diets A and C), whereas hens fed isoflavone aglycons (diet B) significantly increased their egg-laying efficiency. The total egg count and egg yield were significantly higher in hens fed isoflavone aglycons, and their plasma cholesterol concentrations were lower and the eggs laid had a 30% lower yolk cholesterol content. None of these effects were observed with diets containing similar levels of isoflavone glycosides. These studies recapitulate the clinical effects of soy germ pasta enriched with isoflavone aglycons and lend support to the greater efficacy of a diet rich in isoflavone aglycons.

S-equol, a metabolite of soy isoflavone daidzein transformed by the gut microbiome, is the most biologically potent among all soy isoflavones and their metabolites. Soy isoflavones are phytoestrogens and exert their actions through estrogen receptor-β. Epidemiological studies in East Asia, where soy isoflavones are regularly consumed, show that dietary isoflavone intake is inversely associated with cognitive decline and dementia; however, randomized controlled trials of soy isoflavones in Western countries did not generally show their cognitive benefit. The discrepant results may be attributed to S-equol production capability; after consuming soy isoflavones, 40-70% of East Asians produce S-equol, whereas 20-30% of Westerners do. Recent observational and clinical studies in Japan show that S-equol but not soy isoflavones is inversely associated with multiple vascular pathologies, contributing to cognitive impairment and dementia, including arterial stiffness and white matter lesion volume. S-equol has better permeability to the blood-brain barrier than soy isoflavones, although their affinity to estrogen receptor-β is similar. S-equol is also the most potent antioxidant among all known soy isoflavones. Although S-equol is available as a dietary supplement, no long-term trials in humans have examined the effect of S-equol supplementation on arterial stiffness, cerebrovascular disease, cognitive decline, or dementia.

Soy consumption has health benefits, but the relationship between soy and uric acid remains uncertain. This meta-analysis and systematic review evaluated the effects of soy intake on plasma uric acid.

PubMed, Embase, CNKI, and the Cochrane Library were searched for studies evaluating the effects of soy, soy products, soy protein, and soy isoflavones on uric acid levels. The primary outcome was serum or plasma uric acid concentration. Study quality was evaluated by the Cochrane Collaboration and SYRCLE risk-of-bias tools.

A total of 17 studies were included. Qualitative analysis of three human clinical studies of acute effects revealed that soy consumption increased serum uric acid concentration; however, soy-derived products, including tofu, bean curd cake, and dried bean curd sticks, had no significant effect on serum uric acid. A meta-analysis of five long-term human studies (10 data sets) revealed that soy protein and soy isoflavones had no significant effects on uric acid levels [weighted mean difference (WMD) = -2.11; 95% confidence interval (CI): -8.78, 4.55; p = 0.53]. However, most epidemiological data revealed that soy intake is inversely associated with uric acid levels. Meta-analysis of nine animal trials (29 data sets) revealed that soy protein and soy isoflavones significantly reduced serum uric acid concentrations (vs. controls; MD = -38.02; 95% CI: -50.60, -25.44; p < 0.001).

Soy and its products have different effects on serum uric acid. Soy products like tofu, bean curd cake, and dried bean curd sticks could be high-quality protein sources for individuals with hyperuricemia or gout. It can be beneficial to nutritionists and healthcare decision-makers reconsider their conceptions about the relationship between soy and uric acid levels according to the latest and further scientific study results.

[www.crd.york.ac.uk/PROSPERO], identifier [CRD42022331855].

To explore the association between soy product consumption and the risk of depression in the community.

In 2014, a total of 10,901 older people were recruited from Zhejiang province, China, and completed food frequency interviews. Participants were followed up over the next 6 years, and depression was assessed at each visit. Finally, 6,253 participants were included in the present study. Mixed effects models were performed to analyze the association by multivariate adjustments for potential confounders.

Over four-fifths of the eligible participants took soy food at least one day per week. The mixed effects model has shown the adjusted odds ratios (95% CI) of high-frequency consumers (4-7 days per week) were 0.46 (0.39-0.54) for depression with a cut-off score of 5, compared with non-consumers.

More frequent soy product consumption was associated with a lower risk of depression.

Soy is a hotly debated and widely discussed topic in the field of nutrition. However, health practitioners may be ill-equipped to counsel clients and patients about the use of soyfoods because of the enormous, and often contradictory, amount of research that has been published over the past 30 years. As interest in plant-based diets increases, there will be increased pressure for practitioners to gain a working knowledge of this area. The purpose of this review is to provide concise literature summaries (400-500 words) along with a short perspective on the current state of knowledge of a wide range of topics related to soy, from the cholesterol-lowering effects of soy protein to the impact of isoflavones on breast cancer risk. In addition to the literature summaries, general background information on soyfoods, soy protein, and isoflavones is provided. This analysis can serve as a tool for health professionals to be used when discussing soyfoods with their clients and patients.

Genistein is one of the numerous recognized isoflavones that may be found in a variety of soybeans and soy products, including tofu and tofu products. The chemical name for genistein is 4', 5, 7-trihydroxyisoflavone, and it is found in plants. In recent years, the scientific world has become more interested in genistein because of its possible therapeutic effects on many forms of cancer. It has been widely investigated for its anticancer properties. The discovery of genistein's mechanism of action indicates its potential for apoptosis induction and cell cycle arrest in gastrointestinal cancer, especially gastric and colorectal cancer. Genistein's pharmacological activities as determined by the experimental studies presented in this review lend support to its use in the treatment of gastrointestinal cancer; however, additional research is needed in the future to determine its efficacy, safety, and the potential for using nanotechnology to increase bioavailability and therapeutic efficacy.

High phytoestrogen intake during adolescence is associated with a reduced risk of breast cancer. Breast density (BD) is a strong predictor of breast cancer and can be considered an early marker. We aim to assess the association between the mean habitual intake of isoflavones, lignans, and total phytoestrogens intake during puberty until 2 years after menarche onset and absolute fibroglandular volume (AFGV) and percentage of fibroglandular volume (%FGV) in Hispanic girls at the end of puberty.

Longitudinal study set up in the Growth and Obesity Chilean Cohort Study (GOCS). We included 329 girls with dietary data (multiple 24-hours recalls) from puberty until 2 years after menarche onset (81% had 2-4 recalls). Two international datasets were used to estimate isoflavones, lignans, and total phytoestrogens in the diet. Breast composition was measured by dual energy X-ray absorptiometry at 2 years after menarche. Multiple linear regression models were used to assess the association between isoflavones, lignans, and total phytoestrogens intake and AFGV and %FGV.

The average total phytoestrogen intake was 1 mg/day and %FGV was 50.7% (SD = 15.2) and AFGV 218.8 cm3 (SD = 79.3). An inverse association was found between consumption of isoflavones and AFGV, as well as, with total phytoestrogens [Q4 vs. Q1 adjusted model ß = -49.2 cm3; 95% CI (-85.5 to -13.0)].

Girls with a higher intake of total phytoestrogens and isoflavones during puberty until 2 years after menarche onset had significantly lower AFGV.

Although the intake of phytoestrogens is low in Western populations, higher consumption of them during a critical period of life like puberty could be beneficial to reduce breast cancer during adulthood.

Soybean processing waste (SPW) has potential as a sustainable source of phytochemicals and functional foods. A variety of phytochemicals, nutrients, and minerals have been characterized from SPW using various analytical methods. SPW utilization strategies may provide a new way to increase production of bioactive compounds, nutritional supplements, and cosmetic ingredients. SPW has the potential for value-added processing, to improve commercial use, and to lower environmental pollution through proper use. Okara, a byproduct generated during soybean processing of tofu and soy milk, is rich in dietary fiber, isoflavones, and saponins. Isoflavones, an important class of biologically active compounds owing to their multifunctional and therapeutic effects, are extracted from SPW. Further, studies have shown that okara has potential prebiotic and therapeutic value in lowering the risk of noncommunicable diseases. Therefore, in this review, we focus on several extraction methods and pharmacotherapeutic effects of different SPWs. Their effective uses in functional foods, nutraceuticals, and health applications, as biocatalysts, and as value-added resources have been discussed.

Feeding a growing global population with projected rising socioeconomic status will require additional sources of calories and especially protein. These sources need to align with the Sustainable Development Goals established by the Food and Agriculture Organization of the United Nations. The soybean is uniquely positioned to meet this challenge based on the following criteria: (1) Global soybean production exceeds by ~4 times the production of all pulses combined (2) Soybeans are higher in protein than other legumes and soy protein quality is similar to animal protein quality (3) Soybeans are an excellent source of healthy fat, including both essential fatty acids (4) Soybeans, like other legumes, symbiotically fix atmospheric nitrogen thereby reducing the need for fertilizer inputs (5) Greenhouse gas emissions per unit protein are lower than for nearly all other foods (6) Soybeans, like other legumes, are also recognized as an affordable food that can be incorporated into diverse diets regardless of economic standing and (7) The range of foods produced from soybeans constitutes an important position in historic and contemporary cuisines, cultures and emerging consumer trends for plant-based protein. Although most soybeans are currently used for animal feed, soybean use is dictated by consumer demand. Therefore, soybeans are well positioned to meet future global needs for energy and protein. Armed with this knowledge, health professionals can feel justified in encouraging greater consumption of soyfoods for both personal and planetary reasons.

With the rising number of people living with dementia, the interest in modifiable risk factors including dietary intake for dementia is increasing. Although there is a growing body of evidence investigating soy's health effects, the direction and strength of the association between soy consumption and risk of dementia and cognitive decline are still uncertain. Thus, we aimed to review the evidence linking soy consumption to dementia and cognitive function.

Some studies showed that higher intake of total soy products was associated with a lower risk or prevalence of cognitive impairment. Some studies pointed to an inverse association between higher tofu consumption and cognitive function, whereas a higher intake of soybean was associated with better cognitive function.

Previous studies are scarce and have provided contradictory results. Soy is a high-protein alternative to red meat and processed meat. Further studies are needed to clarify the safety and potential preventive effects particularly in healthy populations before clinical disease manifestation and irreversible injury have occurred.