Isoflavone Intake Research Articles

A Systematic Review and Meta-Analysis of the Effects of Dietary Isoflavones on Female Hormone-Dependent Cancers for Benefit-Risk Evaluation.

Female hormone-dependent cancers depend on estrogen for their growth. Numerous studies have explored the antitumor effect of dietary isoflavones on female hormone-dependent cancers. Still, few clinical evidence supports the use of isoflavones in female hormone-dependent cancer patients. This study was performed to examine the impact of dietary isoflavones on tumor growth of female hormone-dependent cancers and accelerate the transformation of research from bench to bedside. We searched PubMed Medline, Web of Science, and Google Scholar for relevant articles related to the effect of dietary isoflavone on tumor growth of experimental animal models of female hormone-dependent cancers from 1998 to 2024. The effects of dietary isoflavones on tumor growth were analyzed between the control and treatment groups using comprehensive meta-analysis software (CMA). We included 30 studies describing tumor growth focused on female hormone-dependent cancer types, including breast, ovarian, and uterine cancers. Overall, a pooled analysis revealed that dietary isoflavones reduced tumor volume (Hedge's g = -1.151, 95% CI = -1.717 to -0.585, p = 0.000) and tumor weight (Hedge's g = -2.584, 95% CI = -3.618 to -1.549, p = 0.000). On the other hand, dietary isoflavones increased tumor area (Hedge's g = 1.136, 95% CI = 0.752 to 1.520, p = 0.000). Dietary isoflavones have potential benefits and risks in female hormone-dependent cancers. Therefore, caution should be exercised when considering the intake of dietary isoflavones in female hormone-dependent cancer patients, particularly in the form of supplements.

The association between dietary polyphenol intake and the odds of metabolic syndrome

Oxidative stress plays a role in the pathophysiology of metabolic syndrome (MetS), and one of the most important features of polyphenols is their antioxidant properties. However, there is no universal consensus on the effectiveness of polyphenols in treating Mets. Therefore, the present study aimed to investigate the association between polyphenols and MetS in an Iranian sample. This cross-sectional study was conducted on an adult population sample from Shiraz, in southern Iran. MetS was calculated using the criteria of the Adult Treatment Panel III (ATP III), which defines MetS as the presence of three or more of the specified risk factors. A validated food frequency questionnaire (FFQ) was used to measure the participant’s food intake. The association between polyphenol intake and the odds on MetS and its components was assessed using logistic regression. In both univariate and multivariate models, the association between polyphenol intake and the risk of MetS was not significant. However, after adjusting for potential confounders in the multivariate model, each unit change in flavonol, flavanone and isoflavones intake was associated with a lower, higher, and higher odds of MetS, respectively (flavonols: odds ratio (OR) = 0.926, 95% confidence interval (CI) 0.891–0.963, P < 0.001—flavanones: OR = 1.007, 95% CI: 1.001–1.014, P = 0.034—isoflavones: OR = 4.920, 95% CI: 1.057–22.894, P = 0.042). Additionally, no significant association was found between polyphenol intake and the risk of MetS components. However, in the multivariate model, after adjusting for potential confounders, a significant association was observed between polyphenol intake and lower odds of high waist circumference (OR = 0.998, 95% CI: 0.996–0.999, P = 0.032). The present study did not reveal a significant association between overall polyphenol intake and the odds of MetS. However, certain subclasses of polyphenols appear to be associated with the likelihood of MetS and its components.

The association between dietary flavonoid intake and frailty risk among middle-aged and elderly US adults: A nationally representative study

Given the global ageing population, exploring potential dietary prevention strategies to reduce the public health burden of frailty is critically important. Dietary flavonoids offer multiple health benefits; however, there is a scarcity of research evidence regarding their association with the risk of frailty in middle-aged and older adults. This study aimed to assess the association between dietary flavonoid intake and frailty risk among middle-aged and older U.S. adults and to analyse the potential roles of different flavonoid subclasses. This study involved 9063 participants aged ≥40 years. Frailty was evaluated using a frailty index, and flavonoid intake was estimated through two 24-h dietary recalls. Analyses were carried out via multivariable logistic regression, restricted cubic spline models, weighted quantile sum regression, and quantile g-computation models. Additionally, subgroup analyses and interaction tests were conducted for age and gender. The results indicated that higher intakes of total flavonoids and subclasses (anthocyanidins, flavan-3-ols, flavanones, flavones, flavonols) were significantly associated with a lower prevalence of frailty, but isoflavone intake was not associated with frailty. A nonlinear, L-shaped dose-response relationship was observed between total flavonoids and frailty risk. Flavonols and flavanones were identified as the main contributors to the overall effect. Age influenced the association between dietary flavonoids and frailty, with middle-aged adults benefiting more than older adults. This study provides new evidence supporting an inverse association between dietary flavonoid intake and frailty risk, especially for foods rich in flavonols and flavanones.

8648 Association of isoflavone intake and age at natural menopause

Abstract Disclosure: M. Mitsunami: None. E.R. Bertone-Johnson: None. A. Eliassen: None. J.E. Chavarro: None. Introduction: Isoflavones, a type of phytoestrogens found mainly in soy and legumes, are structurally similar to estrogens and are consumed at a relatively high rate by Asian populations with an average intake of approximately 15-40 mg/d for isoflavone. They have been reported to alleviate menopausal symptoms, such as hot flashes, suggesting that isoflavones may be biologically active in a low-estrogen environment. Previous studies have reported inconsistent associations between the intake of soy and isoflavones and age at natural menopause. Therefore, our aim was to test the hypothesis that higher isoflavone intake is related to higher age at natural menopause. Methods: We followed 85,810 premenopausal women (mean [SD], 36.5 [4.7] year) who completed a previously validated food frequency questionnaire, had not been diagnosed with cancer, and did not undergo any menopausal hormone therapy as of 1991. Diet was assessed every 4 years. Isoflavone intake was estimated from these reports. Participants self-reported their menopausal status and the type of menopause (natural, surgical, and radiation or chemotherapy) every 2 years. We used proportional hazard regression models with age in months to evaluate the relation of isoflavone intake with age at natural menopause where natural menopause was the study outcome and menopause due to surgery, radiation, or chemotherapy were censoring events. We used restricted cubic splines to assess the possibility of non-linear relations between isoflavone intake and age at menopause using the U.S. average isoflavone intake (0.8mg/d) as a reference while adjusting for potential confounders, including age at menarche, BMI, race/ethnicity, smoking status, physical activity, parity, breastfeeding, time to regular menstrual cycle, energy intake, and two dietary factors identified by principal component analysis. Results: Over 1,079,608 person-years, we observed 37,438 cases of natural menopause. Soy products contributed approximately half of isoflavone intake. There was a non-linear association between isoflavone intake and age at natural menopause (p&amp;lt;0.001). Women with isoflavone intakes below the U.S. national average were more likely to experience earlier onset menopause. Conversely, in women with intakes above the national average, the risk of menopause decreased with increasing isoflavone intakes, albeit plateauing at intakes of approximately 3-4mg/d (90-95th percentile of observed distribution). There was a suggestion of a positive association between isoflavone intake and earlier onset menopause for intakes above the 99th percentile of the observed distribution (∼14 mg/d). Conclusion: This study suggests a non-linear relation between isoflavone intake and age at natural menopause with a potential later onset of menopause at intake levels higher than typical in the US diet but lower than those typically observed in East Asia. Presentation: 6/2/2024

Equol Nonproducing Status as an Independent Risk Factor for Acute Cardioembolic Stroke and Poor Functional Outcome.

Background/Objectives: Equol has protective effects against coronary artery disease and dementia by strongly binding to estrogen receptor beta, whereas the intake of soy isoflavone alone does not always confer such protective effects. Equol production is completely dependent on the existence of equol-producing gut microbiota. The effects of equol-producing status on the cerebrovascular diseases remain unclear. The current study was aimed to investigate the association of equol-producing status with the development of stroke and its neurological prognosis. Methods: Frequencies of equol producers were compared between healthy subjects (HS) registered in the Suita Study and patients with acute stroke admitted to our stroke center from September 2019 to October 2021 in a retrospective cohort study. Results: The proportion of HSs and patients with ischemic stroke who were equol producers did not significantly differ (50/103 [48.5%] vs. 60/140 [42.9%], p = 0.38). However, cardioembolic stroke was significantly associated with low a prevalence of equol producers (adjusted odds ratio [aOR] 0.46, 95% confidence interval [CI] 0.21-0.99, p = 0.05). A higher left atrial volume index was observed in equol nonproducers (46.3 ± 23.8 vs. 36.0 ± 11.6 mL/m2, p = 0.06). The equol nonproducers had a significantly higher prevalence of atrial fibrillation than the equol producers (27.5% vs. 13.3%, p = 0.04). Furthermore, the equol producers exhibited a significantly favorable functional outcome upon discharge (aOR 2.84, 95% CI 1.20-6.75, p = 0.02). Conclusions: Equol is a promising candidate for interventions aiming to reduce the risk of CES and atrial dysfunction, such as atrial fibrillation and improve neurological prognosis after ischemic stroke.

Effect of Isoflavone on Muscle Atrophy in Ovariectomized Mice.

Sarcopenia, characterized by muscle mass decline due to aging or other causes, is exacerbated by decreased estrogen levels after menopause in women. Isoflavones, a class of flavonoids acting on estrogen receptors, may have beneficial effects on metabolic disorders. We examined these effects in ovariectomized mice fed a high-fat, high-sucrose diet (HFHSD). At 7 weeks old, female C57BL6/J mice (18-20 g, n = 12) underwent bilateral ovariectomy (OVX), and were then fed a high-fat, high-sucrose diet starting at 8 weeks of age. Half of the mice received isoflavone water (0.1%). Metabolic analyses, including glucose and insulin tolerance tests, were conducted. Muscle analysis involved grip strength assays, next-generation sequencing, quantitative RT-PCR, and western blotting of skeletal muscle after euthanizing the mice at 14 weeks old. Additionally, 16S rRNA gene sequence analysis of the gut microbiota was performed. The results demonstrated that isoflavone administration did not affect body weight, glucose tolerance, or lipid metabolism. In contrast, isoflavone-treated mice had higher grip strength. Gene expression analysis of the soleus muscle revealed decreased Trim63 expression, and western blotting showed inactivation of muscle-specific RING finger protein 1 in isoflavone-treated mice. Gut microbiota analysis indicated higher Bacteroidetes and lower Firmicutes abundance in the isoflavone group, along with increased microbiota diversity. Gene sets related to TNF-α signaling via NF-κB and unfolded protein response were negatively associated with isoflavones. Isoflavone intake alters gut microbiota and increases muscle strength, suggesting a potential role in improving sarcopenia in menopausal women.

PGC1α in Skeletal Muscle Mediates Anti-Obesity Effects of Soy Isoflavones.

Obesity, a factor increasing the risk of metabolic diseases such as type 2 diabetes, dyslipidemia, and hypertension, can be reduced by the intake of soy isoflavones. In this study, we investigated whether skeletal muscle PGC1α, a transcriptional activator known to promote a variety of exercise-related metabolic processes, is involved in the anti-obesity effects of soy isoflavones using skeletal muscle-specific PGC1α knockout mice. The results showed that the intake of soy isoflavones reduced white adipose tissue weight and increased expression of energy metabolism-related genes such as mitochondrial function, lipolysis, and fatty acid oxidation in skeletal muscle. However, these effects were not observed in skeletal muscle-specific PGC1α knockout mice. In C2C12 myoblasts with overexpressing PGC1α, soy isoflavone treatment increased energy-metabolism related genes. Therefore, PGC1α of skeletal muscle is likely to be involved in the anti-obesity effects of soy isoflavones.

Dietary Isoflavones Intake and Gastric Cancer.

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.

Dietary flavonoid intake and risk of hormone-related cancers: A population-based prospective cohort study

BackgroundDietary flavonoids may have potential effects on hormone-related cancers (HRCs) due to their anti-cancer properties via regulating hormones and suppressing inflammation and oxidative stress. We aimed to examine the association of flavonoid intake with risks of HRCs and whether this association was mediated by blood biomarkers involved in biological mechanisms. MethodsThis prospective cohort study from UK Biobank included 187,350 participants free of cancer when the last dietary recall was completed. The dietary intakes of flavonoids and subclasses were assessed using 24-hour dietary recalls. Venous blood was collected at baseline and assayed for biomarkers of inflammation, hormones, and oxidative stress. Hazard ratios (HR) and 95 % confidential intervals (CI) for the associations between flavonoid intake and HRCs risk were estimated by the cause-specific Cox proportional hazards model. The role of blood biomarkers in the flavonoids-HRCs association was investigated through mediation analysis. ResultsOver a median follow-up of 9.5 years, 3,392 female breast cancer, 417 ovarian cancer, 516 endometrial cancer, 4,305 prostate cancer, 45 testicular cancer, and 146 thyroid cancer cases were documented. Compared to the lowest quintile, multivariable-adjusted HRs (95 % CIs) in the highest quintile of total flavonoid intake were 0.89 (0.80–0.99) for breast cancer, 0.68 (0.50–0.92) for ovarian cancer, and 0.88 (0.80–0.98) for female-specific cancers. For subclasses, intakes of flavonols and anthocyanidins were inversely associated with the risk of female-specific cancers (Ptrend <0.05). Anthocyanidin intake was positively related to prostate cancer risk, whereas isoflavone intake was inversely linked to thyroid cancer risk (Ptrend <0.05). Additionally, certain biomarkers of inflammation, hormones and oxidative stress jointly mediated the association of flavonoid intake with the risk of female-specific cancers and prostate cancer. ConclusionsOur findings highlighted the importance of dietary flavonoids for the prevention of HRCs in the general population, providing epidemiological evidence for dietary guidelines.

Urinary Equol and Equol-Predicting Microbial Genera Are Favorably Associated with Body Fat Measures among Chinese Adults

BackgroundMany studies have investigated the intake of dietary isoflavones in relation to obesity risk, whereas the association using objective biomarkers of isoflavones, particularly equol (a gut-derived metabolite of daidzein with greater bioavailability than other isoflavones) has been less studied. In addition, the associations between equol and gut microbiota profile at the population level remain to be fully characterized. ObjectivesWe aimed to identify equol-predicting microbial species and to investigate the associations of equol-predicting microbial species and urinary excretion of isoflavones including glycitein, genistein, daidzein, and equol with diverse obesity markers in free living-individuals. MethodsIn this 1-y longitudinal study of 754 community-dwelling adults, urinary isoflavones, fecal microbiota, height, weight, and circumferences of waist and hip were measured at baseline and again after 1 y. Liver fat [indicated by the controlled attenuation parameter (CAP)] and other body composition were also measured after 1 y. Linear models and linear mixed-effects models were used to analyze the associations for single measure and repeated measures, respectively. ResultsAmong 305 participants (median age: 50 y, IQR, 37–59 y) including 138 males and 167 females, higher urinary excretion of equol was associated with lower CAP (β = −0.013, P < 0.001) and body fat mass (β= −0.014, P = 0.046). No association was found between any other urinary isoflavones and obesity markers (all P > 0.05). We identified 21 bacterial genera whose relative abundance were positively associated with urinary equol concentrations (all Pfalsediscovery rate < 0.05), and constructed an equol-predicting microbial score to reflect the overall equol-producing potential of host gut microbiota. This score was inversely associated with CAP (β = −0.040, P = 0.011). ConclusionsHigh urinary equol concentrations and equol-predicting microbial species could be favorably associated with liver fat and other obesity markers.

Urinary Equol and Equol-Predicting Microbial Species Are Favorably Associated With Cardiometabolic Risk Markers in Chinese Adults.

The association between soy isoflavones intake and cardiometabolic health remains inconclusive. We investigated the associations of urinary biomarkers of isoflavones including daidzein, glycitein, genistein, equol (a gut microbial metabolite of daidzein), and equol-predicting microbial species with cardiometabolic risk markers. In a 1-year study of 305 Chinese community-dwelling adults aged ≥18 years, urinary isoflavones, fecal microbiota, blood pressure, blood glucose and lipids, and anthropometric data were measured twice, 1 year apart. Brachial-ankle pulse wave velocity was also measured after 1 year. A linear mixed-effects model was used to analyze repeated measurements. Logistic regression was used to calculate the adjusted odds ratio (aOR) and 95% CI for the associations for arterial stiffness. Each 1 μg/g creatinine increase in urinary equol concentrations was associated with 1.47%, 0.96%, and 3.32% decrease in triglycerides, plasma atherogenic index, and metabolic syndrome score, respectively (all P<0.05), and 0.61% increase in high-density lipoprotein cholesterol (P=0.025). Urinary equol was also associated with lower risk of arterial stiffness (aOR, 0.28 [95% CI, 0.09-0.90]; Ptrend=0.036). We identified 21 bacterial genera whose relative abundance was positively associated with urinary equol (false discovery rate-corrected P<0.05) and constructed a microbial species score to reflect the overall equol-predicting capacity. This score (per 1-point increase) was inversely associated with triglycerides (percentage difference=-1.48%), plasma atherogenic index (percentage difference=-0.85%), and the risk of arterial stiffness (aOR, 0.27 [95% CI, 0.08-0.88]; all P<0.05). Our findings suggest that urinary equol and equol-predicting microbial species may improve cardiometabolic risk parameters in Chinese adults.

Consumption of soya isoflavones improved polycystic ovary syndrome-associated metabolic disorders in a rat model.

Polycystic ovary syndrome is associated with increased risks for certain metabolic disorders such as insulin resistance, non-alcoholic fatty liver disease and suppressed ovarian follicular development. This study aimed to examine whether soya isoflavones (ISF) mitigate these polycystic ovary syndrome-associated metabolic disorders in a rat model. Weanling Sprague-Dawley female rats were randomly divided into six groups and were treated with either 0 or 83 µg/d dihydrotestosterone (DHT) to induce polycystic ovary syndrome and fed diets containing 0, 0·5, or 1 g ISF/kg diet for 8 weeks. DHT treatment increased food intake, body weight gain (P < 0·001), percentage of primordial follicles (60 % v. 50·9 %, P < 0·05) and accumulation of lipid droplets in the livers. It also elevated serum total cholesterol, free cholesterol, TAG, NEFA and leptin and hepatic total cholesterol and NEFA. Additionally, DHT treatment reduced the percentage of primary follicles (13·8 % v. 30·2 %, P < 0·05), ovary weight and length (P < 0·001), as well as insulin sensitivity (P < 0·01) compared with the Control. ISF intake at 1 g/kg reduced body weight gain, serum total cholesterol, free cholesterol, NEFA, leptin and hepatic TAG and DHT-induced insulin resistance (P < 0·01). ISF intake at both levels decreased DHT-induced lipid droplet accumulation in the livers and changes in the percentages of primordial and primary follicles. Dietary soya ISF alleviated DHT-induced body weight gain, insulin resistance and hepatic lipid droplet accumulation, as well as suppressed ovarian follicular development. This suggests that the consumption of soya foods or ISF supplements may be beneficial for individuals with polycystic ovary syndrome, mitigating the associated metabolic disorders such as diabetes and non-alcoholic fatty liver disease.

Dietary isoflavone intake is inversely associated with remnant cholesterol in US adults: A cross-sectional study

BackgroundSeveral studies have shown that dietary isoflavones are negatively correlated with total cholesterol and low-density lipoprotein cholesterol. However, few studies have investigated the link between dietary isoflavones and remnant cholesterol (RC). ObjectivesWe used the National Health and Nutrition Examination Survey (NHANES) database to explore the association between dietary isoflavone intake and RC. MethodsA cross-sectional study was conducted with 4731 participants aged ≥ 20 years from the 2007–2008, 2009–2010, and 2017–2018 NHANES databases. We adopted univariate and multiple linear regression analysis and restricted cubic spline (RCS) to assess the relationship between dietary isoflavone intake and RC. Moreover, we conducted stratified and interaction analyses to ensure the stability of the results and identify specific populations. ResultsThe weighted multifactor linear regression model showed a negative correlation between dietary isoflavone intake and remnant cholesterol (Model 2, β = -0.049, 95% CI: (-0.096, -0.002), P = 0.040). The RCS analysis indicated that there was an L-shaped negative correlation between dietary isoflavone intake and RC (P-value for non-linearity was 0.0464). Stratified analyses showed the inverse relationship between dietary isoflavone intake and RC persisted in most subgroups and there was no interaction except for the recreational activity group. ConclusionsOur study found a non-linear and negative association between dietary isoflavone intake and RC in US adults, so we hypothesized that consuming an isoflavone-rich diet may help reduce blood RC and further reduce the risk of cardiovascular disease.

Traditional and Domestic Cooking Dramatically Reduce Estrogenic Isoflavones in Soy Foods.

Soybean is a pulse which has considerable nutritional value due to its high protein, fibers and polyunsaturated fatty acid (PUFA) contents. It also contains phytoestrogenic compounds that definitely hinder its recommendation for general consumption. Contrary to ancient times, when soybeans were boiled, modern commercial soy foods can contain up to 150 mg/100g of estrogenic isoflavones. Interestingly, current estimations of isoflavone intake in the literature do not distinguish between the origins of soy food, i.e., whether it is homemade or commercial. As a result, the isoflavone exposure in Asian countries may well be overestimated. This study aims to demonstrate, based on step-by-step monitoring of isoflavones, that traditional and domestic treatments, leveraging isoflavones water-solubility, can indeed significantly reduce their content in soy foods. Indeed, when compared to commercial foods, the isoflavone content was found to be 20, 2.6, 4.5 and 9.8 times lower in "homemade" soy juice, tofu, tempeh and miso, respectively. Additionally, water soaking was found to reduce the isoflavones levels in soy-textured proteins by more than 70%. Hence, this simple process has the potential to help drastically reduce overall xenoestrogens exposure. This study could serve as a basis for establishing the isoflavones Reference Dose and issuing food safety guidelines.

Changes in the consumption of isoflavones, omega-6, and omega-3 fatty acids in women with metastatic breast cancer adopting a whole-food, plant-based diet: post-hoc analysis of nutrient intake data from an 8-week randomized controlled trial.

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.

Perspective: Observational Studies Involving Low-Soy Intake Populations Have Limited Ability for Providing Insight into the Health Effects of Soybean Isoflavones

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 effect of soy isoflavones on non-alcoholic fatty liver disease and the level of fibroblast growth factor-21 and fetuin A

A two-arm randomized open labeled controlled clinical trial was conducted on 50 patients with non-alcoholic fatty liver disease (NAFLD). Subjects were randomized to either receive two tablets of soy isoflavone (100 mg/day) or placebo. At week 12, the serum levels of alanine amino transferase (ALT), aspartate amino transferase (AST) and controlled attenuation parameter (CAP) score were significantly decreased only in the soy isoflavone group (P < 0.05). A significant decline in the gamma glutamyl transferase (GGT) level was observed only in the placebo group (P = 0.017). A significant increase in the serum level of fetuin A was shown in both groups at the end of the trial with a significantly greater increment in the soy isoflavone group compared to the placebo group (P < 0.05). The changes in the serum level of FGF-21 were not significant in any of the two groups. Steatosis grade significantly improved only in the soy isoflavone group (P = 0.045). There was no significant change in the fibrosis grade in the groups. Soy isoflavone intake led to a decrease in ALT, AST, CAP score, steatosis grade and an increase in the level of fetuin A. However, no significant changes were observed in the fibrosis grade and serum levels of GGT and FGF-21.

The Probable Impact of Soy Isoflavones in Bone Fracture Downturn: A Systematic Review

Background: There is a direct relationship between taking soy isoflavones and higher bone density, but there is a paucity of studies examining the relationship between flavonoid consumption and fracture risk. This study aimed to assess the bone fracture and its relationship to soy product intake by performing a systematic review. Methods: Scopus, PubMed, and Web of science were searched to find studies on the effect of soy isoflavones on bone fracture, without any time and language of publication restrictions. Key words of SoyMilk, soymilk, soybeans, soybean, soy, soya, Isoflavones, Isoflavone, ipriflavone, equol, genistein, daidzein, glycitin, fractures, and broken bone were used. Results: From a total of 1675 articles, 27 studies (cross-sectional studies (n=1), case-control studies (n=1), cohort (n=11), and randomized control trials (n=14)) were identified, and their quality was assessed. Eighteen studies highlighted mainly positive results in preventive influence of soy bone fractures. Two papers reported a positive effect was observed in men with cancer. No significant association was found between soy intake and bone prevention fracture in eight distinct papers. Conclusion: Intake of soy isoflavones can make a significant preventive effect on bone fracture; however, the results of some studies are controversial. Therefore, it is necessary to survey more studies to identify the relationship between isoflavones and bone fracture.

Dietary Flavonoid Intake and Risk of Mild Cognitive Impairment in the Elderly: A Case-Control Study

Background: This study investigates the association between dietary flavonoid intake and the incidence of mild cognitive impairment (MCI) through a matched case-control design. Methods: Dietary intake was assessed using a food frequency questionnaire, comparing the intake of flavonoids between individuals with MCI and those with normal cognitive function. Logistic regression analysis was employed to evaluate the correlation between dietary flavonoid intake and the risk of MCI. Additionally, blood concentrations of S100β, a marker of the blood-brain barrier (BBB) integrity, were measured using electrochemiluminescence immunoassay, and Pearson correlation analysis was conducted to explore the relationship between dietary flavonoid intake and blood S100β levels. Results: Compared to participants with normal cognition, those with MCI had significantly lower dietary intakes of total flavonoids, isoflavones, daidzein, glycitein, genistein, kaempferol, myricetin, flavonols, and anthocyanidins, while the intake of peonidin was significantly higher. Univariate logistic regression analysis indicated that high dietary intake of total flavonoids, isoflavones, daidzein, glycitein, genistein, kaempferol, myricetin, and flavonols was negatively correlated with MCI, whereas peonidin intake was positively correlated with MCI. Multivariate logistic regression analysis confirmed these findings. Pearson correlation analysis revealed a significant negative correlation between dietary intake of kaempferol and myricetin and blood S100β levels. Conclusion: Increasing the dietary intake of total flavonoids, isoflavones, daidzein, glycitein, genistein, and flavonols appears to be a protective factor against MCI, while higher intake of peonidin is associated with an increased risk of MCI. The protective or adverse effects of these flavonoids may not be related to the permeability of the BBB. Myricetin and kaempferol intake may protect cognitive function by maintaining BBB integrity.

Intake of dietary flavonoids in relation to bone loss among U.S. adults: a promising strategy for improving bone health.

Dietary flavonoids have been recommended for improving bone health due to their antioxidant, anti-inflammatory and osteogenic properties. However, the effectiveness of each flavonoid subclass in the prevention and treatment of osteoporosis remains controversial. The objective of the current study was to examine the association between the intake of flavonoid subclasses and bone loss in 10 480 U.S. adults in the National Health and Nutrition Examination Survey. We employed a multinomial logistic regression model to calculate the odds ratios (OR) and 95% confidence intervals (95% CI). The intake of flavones, isoflavones, and flavanones was beneficially associated with osteoporosis (ORQ5 vs. Q1 = 0.44; 95% CI: 0.30-0.64 for flavones; ORQ5 vs. Q1 = 0.53; 95% CI: 0.37-0.77 for isoflavones; ORQ5 vs. Q1 = 0.66; 95% CI: 0.45-0.97 for flavanones). A higher intake of flavones and flavanones was significantly associated with a lower risk of bone loss at the femoral neck rather than the lumbar spine. Notably, stratified analysis showed that genistein had a harmful association with osteopenia in the population with lower serum calcium levels, whereas it had a beneficial association with osteoporosis in the population with higher serum calcium levels. Multiple sensitivity analyses were performed to test the robustness of the results, including subgroup analysis, exclusion of individuals' use of anti-osteoporosis, corticosteroid, and estrogenic medications, adjusting more potential confounders and calculation of the E-value. Overall, incorporating this modifiable diet into an individual's lifestyle could provide potential possibilities to prevent and ameliorate osteoporosis.