Soy Isoflavone Intake Research Articles

The association between soy isoflavone intake and menopausal symptoms after breast cancer diagnosis: a prospective longitudinal cohort study on Chinese breast cancer patients.

This study investigated the association between soy isoflavone intake and menopausal symptoms (MPS) among Chinese women with early stage breast cancer in a prospective cohort study. In an on-going prospective cohort study that involved 1462 Chinese women with early stage breast cancer, MPS were assessed at 18, 36 and 60months after cancer diagnosis using the validated menopausal rating scale (MRS) questionnaire. Daily soy food intake for the previous 12months was assessed at the same time using a validated food frequency questionnaire. The associations between MPS and soy isoflavone intake were evaluated in multivariable logistic regression analyses. The prevalence of MPS was almost the same during the first 60months after cancer diagnosis, which were 64.5%, 65.2%, and 63.9% at 18, 36, and 60months, respectively. Patients with MPS tended to be younger than those without MPS. The intake of soy isoflavones was not associated with the total score of MRS at 18-month follow-up [highest vs lowest tertile, odds ratio (OR) = 1.00, 95% CI 0.75-1.34]. Similarly, no significant association was noted at 36-month (OR = 1.25, 95% CI 0.92-1.69) and 60-month (OR = 1.21, 95% CI 0.84-1.74) follow-up. With regards to specific domain within MRS, the risk of symptoms presenting in somatic domain was higher among breast cancer patients who were in the highest tertile of soy isoflavone intake at 36months post-diagnosis (OR = 1.44, 95% CI 1.07-1.94, P-trend = 0.02), compared with the lowest tertile, where a stronger significant association was noted among patients who were younger than 60years (OR = 1.52, 95% CI 1.05-2.20, P-trend = 0.03) and pre-menopausal (OR = 3.81, 95% CI 1.85-8.11, P-trend < 0.01). The present study provided further evidence that soy isoflavone consumption was not associated with MPS among Chinese breast cancer patients. In fact, patients with higher intake of soy isoflavone have increased risk of experiencing somatic symptoms.

Legume and soy intake and risk of type 2 diabetes: a systematic review and meta-analysis of prospective cohort studies

Previous findings on the associations of legume and soy intake with the risk of type 2 diabetes are conflicting. We aimed to summarize the longitudinal associations between legume and soy intake and risk of type 2 diabetes. We searched for relevant prospective cohort studies in PubMed, EMBASE, and Ovid up to August 2019. Study-specific, multivariable-adjusted RRs and 95% CIs were pooled by random-effects models. We identified 15 unique cohorts including 565,810 individuals and 32,093 incident cases. The summary RRs (95% CIs) of incident type 2 diabetes were 0.95 (0.79, 1.14; NS) for total legumes, 0.83 (0.68, 1.01; NS) for total soy, 0.89 (0.71, 1.11; NS) for soy milk, 0.92 (0.84, 0.99) for tofu, 0.84 (0.75, 0.95) for soy protein, and 0.88 (0.81, 0.96) for soy isoflavones, respectively. High heterogeneity was found for total legumes (I2=84.8%), total soy (I2=90.8%), and soy milk (I2=91.7%). Potential sources of heterogeneity were not evident for total legumes or soy milk, whereas for total soy, geographic location (Asia, United States; P=0.04) and study quality (high, moderate, or low; P = 0.02) significantly predicted heterogeneity. In dose-response analysis, significant linear inverse associations were observed for tofu, soy protein, and soy isoflavones (all P < 0.05). Overall quality of evidence was rated as moderate for total legumes and low for total soy and soy subtypes. Dietary intakes of tofu, soy protein, and soy isoflavones, but not total legumes or total soy, are inversely associated with incident type 2 diabetes. Our findings support recommendations to increase intakes of certain soy products for the prevention of type 2 diabetes. However, the overall quality of evidence was low and more high-quality evidence from prospective studies is needed. This trial was registered as PROSPERO CRD42019126403 (https://www.crd.york.ac.uk/PROSPERO).

Uterine Patterning, Endometrial Gland Development, and Implantation Failure in Mice Exposed Neonatally to Genistein.

Background:Embryo implantation relies on precise hormonal regulation, associated gene expression changes, and appropriate female reproductive tract tissue architecture. Female mice exposed neonatally to the phytoestrogen genistein (GEN) at doses similar to those in infants consuming soy-based infant formulas are infertile due in part to uterine implantation defects.Objectives:Our goal was to determine the mechanisms by which neonatal GEN exposure causes implantation defects.Methods:Female mice were exposed to GEN on postnatal days (PND)1–5 and uterine tissues collected on PND5, PND22–26, and during pregnancy. Analysis of tissue weights, morphology, and gene expression was performed using standard histology, confocal imaging with three-dimensional analysis, real-time reverse transcription polymerase chain reaction (real-time RT-PCR), and microarrays. The response of ovariectomized adults to (E2) and artificial decidualization were measured. Leukemia inhibitory factor (LIF) injections were given intraperitoneally and implantation sites visualized. Gene expression patterns were compared with curated data sets to identify upstream regulators.Results:GEN-exposed mice exhibited reduced uterine weight gain in response to E2 treatment or artificial decidualization compared with controls; however, expression of select hormone responsive genes remained similar between the two groups. Uteri from pregnant GEN-exposed mice were posteriorized and had reduced glandular epithelium. Implantation failure was not rescued by LIF administration. Microarray analysis of GEN-exposed uteri during early pregnancy revealed significant overlap with several conditional uterine knockout mouse models, including Foxa2, Wnt4, and Sox17. These models exhibit reduced endometrial glands, features of posteriorization and implantation failure. Expression of Foxa2, Wnt4, and Sox17, as well as genes important for neonatal uterine differentiation (Wnt7a, Hoxa10, and Msx2), were severely disrupted on PND5 in GEN-exposed mice.Discussion:Our findings suggest that neonatal GEN exposure in mice disrupts expression of genes important for uterine development, causing posteriorization and diminished gland function during pregnancy that contribute to implantation failure. These findings could have implications for women who consumed soy-based formulas as infants. https://doi.org/10.1289/EHP6336

Soy intake and breast cancer risk: a prospective study of 300,000 Chinese women and a dose\u2013response meta-analysis

Epidemiological evidence on the association of soy intake with breast cancer risk is still inconsistent due to different soy intake levels across previous studies and small number of breast cancer cases. We aimed to investigate this issue by analyzing data from the China Kadoorie Biobank (CKB) study and conducting a dose–response meta-analysis to integrate existing evidence. The CKB study included over 300,000 women aged 30–79 from 10 regions across China enrolled between 2004 and 2008, and followed-up for breast cancer events until 31 December 2016. Information on soy intake was collected from baseline, two resurveys and twelve 24-h dietary recalls. We also searched for relevant prospective cohort studies to do a dose–response meta-analysis. The mean (SD) soy intake was 9.4 (5.4) mg/day soy isoflavones among CKB women. During 10 years of follow-up, 2289 women developed breast cancers. The multivariable-adjusted relative risk was 1.00 (95% confidence interval [CI] 0.81–1.22) for the fourth (19.1 mg/day) versus the first (4.5 mg/day) soy isoflavone intake quartile. Meta-analysis of prospective studies found that each 10 mg/day increment in soy isoflavone intake was associated with a 3% (95% CI 1–5%) reduced risk of breast cancer. The CKB study demonstrated that moderate soy intake was not associated with breast cancer risk among Chinese women. Higher amount of soy intake might provide reasonable benefits for the prevention of breast cancer.

Anti-Osteoporotic Effect of Soy Isoflavones Intake on Low Bone Mineral Density Caused by Voluntary Exercise and Food Restriction in Mature Female Rats.

Female athlete triad (FAT) is an interrelationship between menstrual dysfunction, low energy availability with or without eating disorder, and decreased bone mineral density (BMD) in female athletes. The purpose of this study was to investigate whether isoflavone intake can prevent bone loss caused by voluntary wheel running under energy-restricted condition. We used a female rat model of osteoporosis for female athletes established previously. Fourteen female Sprague-Dawley rats (8-wk old) were fed ad libitum and had free access to wheels throughout the study. At 18 wk of age, the rats were divided randomly into the following groups: 1) running control (RC), 2) running energy restriction (RR), and 3) running energy restriction and isoflavone-fed (RR+Iso) groups. The RR group was 30% dietary restricted. The RR+Iso group was 30% dietary restricted and fed the diet containing 0.5% isoflavone powder (Fujiflavone P40). The experimental period lasted 31 wk. At the end of this experiment, BMD of the proximal femur in the RR group was significantly lower than that in the RC group. However, the BMD in the RR+Iso group was not significantly different from that in the RC group. Moreover, the plasma estradiol (E2) level in the RR and RR+Iso groups was significantly lower than that in the RC group. These findings suggest that isoflavone intake inhibited bone loss when the E2 level was low in female mature rat model. Our findings may reveal the possible novel role of isoflavone in osteoporosis among female athletes.

Soy food and isoflavones are not associated with changes in serum lipids and glycohemoglobin concentrations among Japanese adults: a cohort study.

It is unclear whether habitual intake of soy or isoflavones induces long-term changes in the concentrations of blood lipids and glycaemia. We examined the associations of soy food and isoflavone consumption with changes in blood lipids and HbA1c concentrations over 5years among Japanese adults. This cohort study included 7252 subjects with no known history of major chronic disease at baseline. Soy intake was measured using a food frequency questionnaire; while the concentrations of serum lipids and HbA1c were measured using standard laboratory methods. We used multivariable linear mixed-effects models to examine the associations of changes in lipids and HbA1c concentrations with intakes of soy food and isoflavones. Among the participants, mean age was 61years, 67% were females and median intakes of soy and isoflavones were 95.3g/day and 47.4mg/day, respectively. Soy food and isoflavone intakes were not associated with 5-year changes in blood lipids or HbA1c concentrations. However, stratified analyses showed inverse associations between fermented soy intake and serum lipids among obese/overweight subjects. In particular, intake of 20g/day of natto was associated with a reduction of 1.4 (95% CI 0.3, 2.5) mg/dL in TC, 1.5 (95% CI 0.4, 2.6) mg/dL in non-high-density lipoprotein cholesterol, 1.0 (95% CI - 0.0, 2.0) mg/dL in low-density lipoprotein cholesterol and 4.0 (95% CI 0.6, 7.5) mg/dL in triglycerides. Overall, habitual consumption of soy or isoflavones was not associated with changes in serum lipids or HbA1c concentrations. The negative associations between intake of natto and changes in serum lipids among overweight/obese subjects deserve further investigation.

Soy, Soy Isoflavones, and Protein Intake in Relation to Mortality from All Causes, Cancers, and Cardiovascular Diseases: A Systematic Review and Dose–Response Meta-Analysis of Prospective Cohort Studies

ObjectiveWe conducted a systematic review and dose–response meta-analysis of prospective studies to summarize findings on the associations between intakes of soy, soy isoflavones, and soy protein and risk of mortality from all causes, cancers, and cardiovascular diseases. MethodsOnline databases were systematically searched to identify relevant articles published earlier than May 2018. We applied restricted cubic splines using random-effects analysis to assess dose–response associations. Between-study heterogeneity was assessed by I2 value and Cochrane Q test. Potential publication bias was assessed by visual inspection of funnel plots and Begg regression test. ResultsIn total, 23 prospective studies with an overall sample size of 330,826 participants were included in the current systematic review and the meta-analysis. Soy/soy products consumption was inversely associated with deaths from cancers (pooled relative risk 0.88, 95% CI 0.79 to 0.99; P=0.03; I2=47.1%, 95% CI 0.0% to 75.4%) and cardiovascular diseases (pooled effect size: 0.85, 95% CI 0.72 to 0.99; P=0.04; I2=50.0%, 95% CI 0.0% to 77.6%). Such significant associations were also observed for all-cause mortality in some subgroups of the included studies, particularly those with higher quality. In addition, higher intake of soy was associated with decreased risk of mortality from gastric, colorectal, and lung cancers as well as ischemic cardiovascular diseases. Participants in the highest category of dietary soy isoflavones intake had a 10% lower risk of all-cause mortality compared with those in the lowest category. We also found that a 10-mg/day increase in intake of soy isoflavones was associated with 7% and 9% decreased risk of mortality from all cancers and also breast cancer respectively. Furthermore, a 12% reduction in breast cancer death was indicated for each 5-g/day increase in consumption of soy protein. However, intake of soy protein was not significantly associated with all-cause and cardiovascular diseases mortality. ConclusionsSoy and its isoflavones may favorably influence risk of mortality. In addition, soy protein intake was associated with a decreased risk in the mortality of breast cancer. Our findings may support the current recommendations to increase intake of soy for greater longevity.

Dietary Soy Intake Is Inversely Associated with Risk of Type 2 Diabetes in Japanese Women but Not in Men

Whole soy foods, as well as their components, including protein and isoflavones, have garnered attention because they may have beneficial effects against diabetes. We examined associations between the intake of soy foods, soy protein, and soy isoflavones and the risk of diabetes in the Japanese population. This prospective cohort study included 13,521 residents (5883 men and 7638 women; 35-69 y old) of Takayama City, Japan. The subjects responded to a self-administered baseline questionnaire in 1992 and to a follow-up questionnaire seeking information about diabetes in 2002. Their mean ± SD body mass index was 22.6 ± 2.6 kg/m2 (men) and 22.1 ± 2.7 (women). The intakes of total soy foods, fried soy foods, nonfried soy foods, soy protein, and soy isoflavones were estimated through the use of a validated food-frequency questionnaire administered in 1992. Associations between soy intake and the risk of diabetes were evaluated through the use of Cox proportional hazards models incorporating age, education level, physical activity, smoking status, alcohol consumption, history of hypertension, use of vitamin supplements, menopausal status, and dietary factors including glycemic load, total energy, total fat, meat, fruit, vegetables, and coffee. During a 10-y follow-up, 438 participants reported physician-diagnosed diabetes. Women in the highest tertile of intakes of total soy foods, fried soy foods, nonfried soy foods, soy protein, and soy isoflavone had significantly lower HRs, after controlling for covariates, than those with the lowest intakes. For example, HRs were 0.45 (95% CI: 0.30, 0.68; P-trend <0.001) for total soy food intake. In men, there were no significant associations between soy intake and the risk of diabetes. These results suggest that a high soy intake may be associated with a lower risk of diabetes in Japanese women.

Safety and Efficacy Assessment of Isoflavones from Pueraria (Kudzu) Flower Extract in Ovariectomised Mice: A Comparison with Soy Isoflavones.

Numerous Foods with Function Claims that contain the extract of Pueraria flower (kudzu) isoflavones (PFI) are available in the Japanese market. These are labelled with function claims of reducing visceral fat. However, these foods have not undergone proper safety assessment such as the evaluation of their oestrogenic activity and effects on drug-metabolising enzymes (cytochrome P-450: CYP) in the liver. This study evaluated the estrogenic effect and the hepatic CYP activity and mRNA expression in normal female mice as a safety assessment of PFI (Experiment 1). In addition, the bone mineral density and visceral fat weight in ovariectomised mice (OVX) compared to soy isoflavones (SI) was evaluated to assess the efficacy of PFI (Experiment 2). OVX control fed a control diet, OVX fed a PFI diet (the recommended human intake of PFI), OVX fed a PFI20 diet (20- times the recommended PFI), OVX fed an SI diet (the recommended human intake of SI), and OVX fed an SI20 diet (20 -times the recommended intake of SI) for 28 days in Experiment 2. Body, liver, and visceral fat weights were not affected by the PFI, PFI20, SI, or SI20 diets. The hepatic CYP1A and CYP3A activities were elevated by the SI20 treatment. Ovariectomy-induced bone loss was inhibited by the SI20 treatment, but not by the PFI20 treatment. These results suggest that (1) PFI intake in human doses had no oestrogenic properties and did not affect CYP activity in the liver; (2) there was no evidence that PFI affects the amount of visceral fat in OVX mice.

Soy Food Consumption, Exercise, and Body Mass Index and Osteoporotic Fracture Risk Among Breast Cancer Survivors: The Shanghai Breast Cancer Survival Study.

BackgroundBreast cancer survivors have a high incidence of osteoporosis-related fractures; the associated factors are understudied. We investigated incidence of bone fracture and its associations with soy food consumption, exercise, and body mass index among breast cancer survivors.MethodsThis prospective study included 4139 stage 0–III breast cancer patients and 1987 pre-/perimenopausal and 2152 postmenopausal patients. Fractures were assessed at 18 months and at 3, 5, and 10 years after cancer diagnosis. Osteoporotic fractures were defined as fractures caused by falls from standing height and at sites associated with osteoporosis. Exercise and soy isoflavone intake were assessed at 6 and 18 months postdiagnosis. Weight and height were measured at baseline. Lifetable and Cox regression analyses were employed. All statistical tests were two sided.ResultsThe 10-year incidence for osteoporotic fractures was 2.9% and 4.4% for pre-/perimenopausal and postmenopausal patients, respectively. High soy isoflavone intake was associated with reduced risk among pre-/perimenopausal patients (hazard ratio [HR] = 0.22, 95% confidence interval [CI] = 0.09 to 0.53, for soy isoflavone mg/d ≥56.06 vs <31.31; Ptrend < .001) but not among postmenopausal patients (Pinteraction < .01). Overweight (vs normal weight) was a risk factor for pre-/perimenopausal patients (HR = 1.81, 95% CI = 1.04 to 3.14) but not for postmenopausal patients (HR = 0.67, 95% CI = 0.43 to 1.03; Pinteraction = .01). Exercise was inversely associated with osteoporotic fractures in postmenopausal patients (HR = 0.56, 95% CI = 0.33 to 0.97, for metabolic equivalents hours ≥12.6 vs <4.5) following a dose-response pattern (Ptrend = .035), an association not modified by menopausal status.ConclusionsOur findings, especially the novel association of soy food intake with osteoporotic fractures in breast cancer survivors, if confirmed, can help guide future strategies for fracture risk reduction in this vulnerable population.

Compositional and functional differences in human gut microbiome with respect to equol production and its association with blood lipid level: a cross-sectional study

BackgroundGut microbiota affects lipid metabolism interactively with diet. Equol, a metabolite of isoflavones produced by gut bacteria, may contribute substantially in beneficial lipid-lowering effects. This study aimed to examine equol production-related gut microbiota differences among humans and its consequent association with blood lipid levels.ResultsCharacterization of the gut microbiota by deep shotgun sequencing and serum lipid profiles were compared between equol producers and non-producers. Gut microbiota differed significantly at the community level between equol producers and non-producers (P = 0.0062). At the individual level, 32 species associated with equol production were identified. Previously reported equol-producing related species Adlercreutzia equolifaciens and Bifidobacterium bifidum showed relatively higher abundance in this study in equol producers compared to non-producers (77.5% vs. 22.5%; 72.0% vs. 28.0%, respectively). Metabolic pathways also showed significant dissimilarity between equol producers and non-producers (P = 0.001), and seven metabolic pathways were identified to be associated with the equol concentration in urine. Previously reported equol production-related gene sequences in A. equolifaciens 19450T showed higher relative abundance in equol producers than in non-producers. Additionally, we found that equol production was significantly associated with the prevalence of dyslipidemia, including a marginal increase in serum lipids (27.1% vs. 50.0%, P = 0.02). Furthermore, equol production was not determined by intake of soy isoflavones, which suggested that gut microbiota is critical in the equol production process.ConclusionBoth content and functioning of the microbial gut community significantly differed between equol producers and non-producers. Further, equol producers showed lower prevalences of dyslipidemia, which suggests the important role that equol might play in lipid metabolism by gut microbiota.

Soy Isoflavone Supplementation Increases Long Interspersed Nucleotide Element-1 (LINE-1) Methylation in Head and Neck Squamous Cell Carcinoma

Aim: Soy isoflavones have been suggested as epigenetic modulating agents with effects that could be important in carcinogenesis. Hypomethylation of LINE-1 has been associated with head and neck squamous cell carcinoma (HNSCC) development from oral premalignant lesions and with poor prognosis. To determine if neoadjuvant soy isoflavone supplementation could modulate LINE-1 methylation in HNSCC, we undertook a clinical trial.Methods: Thirty-nine patients received 2–3 weeks of soy isoflavone supplements (300 mg/day) orally prior to surgery. Methylation of LINE-1, and 6 other genes was measured by pyrosequencing in biopsy, resection, and whole blood (WB) specimens. Changes in methylation were tested using paired t tests and ANOVA. Median follow up was 45 months.Results: LINE-1 methylation increased significantly after soy isoflavone (P < 0.005). Amount of change correlated positively with days of isoflavone taken (P = 0.04). Similar changes were not seen in corresponding WB samples. No significant changes in tumor or blood methylation levels were seen in the other candidate genes.Conclusion: This is the first demonstration of in vivo increases in tissue-specific global methylation associated with soy isoflavone intake in patients with HNSCC. Prior associations of LINE-1 hypomethylation with genetic instability, carcinogenesis, and prognosis suggest that soy isoflavones maybe potential chemopreventive agents in HNSCC.

Effect of S-equol and Soy Isoflavones on Heart and Brain.

Background: Observational studies in Asia show that dietary intake of soy isoflavones had a significant inverse association with coronary heart disease (CHD). A recent randomized controlled trial (RCT) of soy isoflavones on atherosclerosis in the US, however, failed to show their benefit. The discrepancy may be due to the much lower prevalence of S-equol producers in Westerners: Only 20-30% of Westerners produce S-equol in contrast to 50-70% in Asians. S-equol is a metabolite of dietary soy isoflavone daidzein by gut microbiome and possesses the most anti-atherogenic properties among all isoflavones. Several short-duration RCTs documented that soy isoflavones improves arterial stiffness. Accumulating evidence shows that both atherosclerosis and arterial stiffness are positively associated with cognitive decline/dementia. Therefore, potentially, soy isoflavones, especially S-equol, are protective against cognitive decline/dementia.Methods/Results: This narrative review of clinical and epidemiological studies provides an overview of the health benefits of soy isoflavones and introduces S-equol. Second, we review recent evidence on the association of soy isoflavones and S-equol with CHD, atherosclerosis, and arterial stiffness as well as the association of atherosclerosis and arterial stiffness with cognitive decline/dementia. Third, we highlight recent studies that report the association of soy isoflavones and S-equol with cognitive decline/dementia. Lastly, we discuss the future directions of clinical and epidemiological research on the relationship of S-equol and CHD and dementia.Conclusions: Evidence from observational studies and short-term RCTs suggests that S-equol is anti-atherogenic and improves arterial stiffness and may prevent CHD and cognitive impairment/dementia. Well-designed long-term (≥ 2years) RCTs should be pursued.

Soy Isoflavones and their Effects on Xenobiotic Metabolism.

Soy isoflavones, such as genistein and daidzein, are bioflavonoids found in soy products that are able to interact with various hormones such as estrogen. Epidemiological studies reveal a proper level of isoflavones in diet can prevent many diseases like cancers or diabetes. Therefore, it is important to study the biotransformation and xenobiotic metabolism of soy isoflavones. A systematic review of published studies was carried out to investigate the characterization of isoflavones and their metabolites, sample pretreatment and quantitative analysis of isoflavones, and the influence of soy isoflavones on drug and xenobiotic metabolism. Aglycones with weak estrogen-like activities are the biologically active forms of the soy isoflavones in mammals. The most recent advances including extraction, purification and detection of isoflavones in soybean and soy products are discussed. The effects of soy isoflavones on drug and xenobiotic metabolism involve in regulation of phase I cytochrome P450 (CYPs) enzyme and phase I detoxifying enzymes expression and activity. At the molecular level, soy isoflavones have proved capable of estrogenic/antiestrogenic with tissue-selective, anti-cancer, antiobesity, anti-oxidation, and tyrosine kinase inhibition activities. This review summarized different aspects of soy isoflavones and their molecular mechanisms of pharmacological action on xenobiotic, which demonstrated that soy isoflavones can decrease the incidence of many diseases and benefit for human health. However, since the lack of clinical research for evaluation of the proper dosage of intake of soy isoflavones in diet or adjunctive therapy, there is a need for further studies on the selection of doses, biomedical applications and adverse effects of isoflavones for human health.

Soy Intake and Breast Cancer Risk: A Prospective Study of 300,000 Chinese Women and a Dose-Response Meta-Analysis

Background: Epidemiological evidence on the association of soy intake with breast cancer risk is still inconsistent due to different soy intake levels across previous studies and small number of breast cancer cases. We aimed to investigate this issue by analyzing data from the China Kadoorie Biobank (CKB) study and doing a dose-response meta-analysis to integrate existing evidence. Methods: The CKB study included over 300,000 women aged 30 to 79 from 10 regions across China enrolled between 2004 and 2008, and followed-up for breast cancer events until 31 December 2016. Information on soy intake was collected from baseline, two resurveys and twelve 24-hour dietary recalls. We also searched for relevant prospective cohort studies to do a dose-response meta-analysis. Findings: The mean soy intake was 9.4 mg/day soy isoflavones among CKB women. During 10 years of follow-up, 2,289 women developed breast cancers. The multivariable-adjusted relative risk was 0.98 (95% confidence interval [CI]: 0.80 to 1.20) for the fourth (19.1 mg/day) versus the first (4.5 mg/day) soy isoflavone intake quartile. Meta-analysis of prospective studies found that each 10 mg/day increment in soy isoflavone intake was associated with a 3% (95%CI: 1% to 5%) reduced risk of breast cancer. Interpretation: Soy intake at around 20 mg/day of soy isoflavones was not associated with breast cancer risk among Chinese women. Women might need to consume soy at an amount of i‚³ 35 mg/day soy isoflavones to get benefits (reduced risk by 10%) in preventing breast cancer. Funding: National Natural Science Foundation of China and National Key Research and Development Program. Declaration of Interest: All authors declare: no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. Ethical Approval: The Ethical Review Committee of the Chinese Center for Disease Control and Prevention (Beijing, China) and the Oxford Tropical Research Ethics Committee, University of Oxford (UK) approved the study.

Effects of Intake of Soy and Non-Soy Legume on Serum HDL-Cholesterol Levels

High-density lipoprotein (HDL) has been shown to have a variety of functions that contribute to anti-atherogenesis. Here we review meta-analyses on the effects of intake of soy protein and isoflavones on serum HDL-cholesterol (HDL-C) levels, and we would also review meta-analysis on the effects of intake of non-soy legume on serum HDL-C, to make “Dietary Reference Intake for Japanese 2020”. We searched meta-analyses of randomized, placebo-controlled trials. A search was conducted by using PubMed, Embase and Google Scholar, with the following keywords: soy and HDL and meta-analysis. The search period was comprised from 2007 up to July 2018. We found three meta-analyses about effects of intake of soy protein and isoflavones on HDL-C after 2007. All meta-analyses reported that intake of soy protein and isoflavones was associated with a significant increase of HDL-C. We found the meta-analysis which evaluated effects of intake of non-soy legume on HDL-C, in which a significant association of intake of non-soy legume with HDL-C was not obtained due to a significant heterogeneity of collected data. In conclusion, intake of soy was significantly associated with elevation of HDL-C; however, non-soy consumption was not associated with a significant increase of HDL. J Endocrinol Metab. 2018;8(5):83-86 doi: https://doi.org/10.14740/jem524w

Soy Isoflavone Intake and Bladder Cancer Risk in Japan: From the Takayama Study

Background: There is growing evidence suggesting that soy isoflavones play a protective role in the development of cancer. However, few epidemiological studies have investigated the association between soy isoflavone intake and bladder cancer.Methods: We evaluated the associations of soy and isoflavone intakes with bladder cancer incidence in a population-based prospective study in Japan. Subjects were 14,233 men and 16,584 women age 35 years or older in September 1992. Soy and isoflavone intakes were assessed via a validated food-frequency questionnaire, while controlling for total energy intake. Cancer incidence was mainly confirmed through regional population-based cancer registries. Bladder cancer was defined as code C67 according to the International Classification of Diseases and Health Related Problems, 10th Revision.Results: During mean follow-up of 13.6 years, 120 men and 41 women had developed bladder cancer. After adjustments for multiple confounders, compared with the lowest quartile of soy food intake, the estimated hazard ratios for the second, third, and highest quartiles of soy food intake were 0.74, 0.52, and 0.55, respectively, in men (P-trend: 0.023). The corresponding values were 0.60, 0.75, and 0.64, respectively, in women (P-trend: 0.43). Similar inverse associations were observed between isoflavone intake and bladder cancer risk.Conclusions: A significant decreased risk of bladder cancer was observed among men who had higher intakes of total soy and isoflavones.Impact: Our finding on the potential benefit of consuming soy foods against bladder cancer is promising and warrants further studies. Cancer Epidemiol Biomarkers Prev; 27(11); 1371-5. ©2018 AACR.

Highlights of This Issue

There is growing evidence suggesting that soy isoflavones play a protective role in the development of cancer. However, few epidemiological studies have investigated the association between soy isoflavone intake and bladder cancer. This prospective study in Japan detected a decreased risk of bladder cancer among men who had higher intakes of total soy and isoflavones, suggesting a protective effect of soy isoflavone intake against bladder cancer in men. This finding by Wada and colleagues on the potential benefit of consuming soy foods against bladder cancer is promising and warrants further studies.Americans living in rural communities face many challenges when it comes to receiving adequate cancer care. This has resulted in a growing disparity in mortality and incidence for certain cancers in rural areas when compared to their urban counterparts. In order to understand and improve cancer control in rural communities, the NCI conducted an assessment of the current state of research through a progressive series of portfolio analyses, meetings, and funding opportunity announcements. In this commentary, Kennedy and colleagues provide an overview of the NCI's vision for rural cancer control, and detail recommendations stemming from a recently held meeting to advance rural cancer control research. This commentary also serves as an introduction to the CEBP Focus on Rural Cancer Control, which contains three additional commentaries and six research articles.Human papillomavirus self-sampling is a promising method to improve cervical cancer screening coverage, but not all routine screening non-attenders accept self-sampling. Harder and colleagues investigated determinants of participating in self-sampling among 21,314 non-attenders in a Danish routine screening program who were invited to order a self-sampling test. Information on socio-demographic, health-related, and lifestyle characteristics were obtained from registries and questionnaires. Basic education, low income, non-Western origin, and being unmarried were associated with lower self-sampling participation. Women with prior schizophrenia and long-term screening non-attenders were less likely to participate. The study highlights that although self-sampling can increase cervical cancer screening coverage, certain population groups may remain unscreened.The use of alerts and reminders in the electronic health record has led to increased screening for a variety of conditions. However, implementation of screening recommendations for chronic hepatitis B among foreign-born persons at risk has been suboptimal. Chak and colleagues randomized patients at risk for chronic hepatitis B to receive an electronic medical alert reminding primary care physicians to screen for the virus during clinic visits. The study shows that electronic alerts increase screening for chronic hepatitis B—a condition known to cause liver cancer in affected patients. In the age of digital medicine, the study has broad implications for mass screening of patients at risk for this chronic viral infection.

Habitual consumption of soy protein and isoflavones and risk of metabolic syndrome in adults ≥ 40years old: a prospective analysis of the Korean Multi-Rural Communities Cohort Study (MRCohort).

Although considerable attention has been paid to the potential benefits of soy protein and isoflavones for preventing metabolic syndrome (MetS) and its components, findings linking habitual consumption of these factors to MetS are limited. This study aimed to evaluate the association of MetS incidence with habitual intake of soy protein/isoflavones among Korean men and women aged ≥ 40years old who did not have MetS at baseline (n = 5509; 2204 men and 3305 women). Dietary intake of soy protein/isoflavones at baseline and average consumption during follow-up were used. A significant inverse association between dietary intake and incidence of MetS was found in women (incidence rate ratios, IRR = 0.60, 95% CI = 0.46-0.78, P for trend = 0.0094 for the highest quintile of average soy protein intake compared with the lowest quintile; IRR = 0.57, 95% CI = 0.44-0.74, P for trend = 0.0048 for the highest quintile of average isoflavones intake compared with the lowest quintile). A tendency towards an inverse association was also found in men, although it was not significant for the highest quintile (IRR = 0.80, 95% CI = 0.58-1.11, P for trend = 0.9759, comparing the lowest to the highest quintile of average soy protein intake; IRR = 0.73, 95% CI = 0.53-1.01, P for trend = 0.8956, comparing the lowest to the highest quintile of average isoflavones intake). In terms of individual abnormalities, a significant inverse association was found between soy protein and isoflavones and the incidence of low-high-density lipoprotein cholesterol in both men and women. Abdominal obesity and elevated blood pressure were inversely related to soy protein/isoflavones only in women, and an inverse association of elevated triglyceride appeared only in men. Our findings suggest that habitual intake of soy protein and isoflavones is inversely associated with the risk of MetS and its components. There is likely to be a reverse J-shaped association of average intake with MetS.

Daidzein, its effects on impaired glucose and lipid metabolism and vascular inflammation associated with type 2 diabetes.

Over the last decades, the incidence of type 2 diabetes (T2D) is increasing substantially. Emerging evidences from epidemiological studies have shown the association between higher intake of soy isoflavones and reduced risk of T2D and its associated health risks. Daidzein, a soy isoflavone, has been found to have a promising therapeutic potential in managing T2D pathophysiology. Fermented soybean is the major source of daidzein; however, it can also be formed via the consumption of its glycosylated moiety, daidzin with subsequent hydrolysis by intestinal bacterial enzyme. Many studies reported the prophylactic effect of daidzein on the improvement of hyperglycemia, insulin resistance, dislipidemia, obesity, inflammation, and other complications associated with T2D. The molecular mechanisms underlying the action of daidzein include diverged pathways where daidzein has been shown to interact with several signaling molecules and receptors to achieve desirable effect. Although the specific molecular mechanism is still elusive, further studies are thus needed to understand it in detail. In this review, we discuss the antidiabetic potential of daidzein with respect to the evidences from various clinical, preclinical, and cell culture studies and the underlying molecular mechanism in a precise way to have a comprehensive account on this isoflavone with promising therapeutic potential. © 2018 BioFactors, 44(5):407-417, 2018.