Soy Isoflavone Intake Research Articles

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.

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.

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.

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.

Skeletal Effects of Soy Isoflavone in Humans: Bone Mineral Density and Bone Markers

The potential skeletal effects of soy isoflavones in humans have garnered significant interest owing to their structural resemblance to endogenous estrogen and their potential to impact bone health. This abstract provides a concise overview of the current understanding of the effects of soy isoflavones on bone mineral density (BMD) and bone markers. Numerous studies have investigated the relationship between soy isoflavone consumption and BMD. Some studies have suggested a positive association between soy isoflavone intake and BMD, particularly among postmenopausal women. Isoflavones may exert their effects through estrogen receptor-mediated pathways, potentially mitigating bone loss by reducing osteoclastic activity and promoting osteoblastic functions. However, conflicting results have been reported, with certain studies demonstrating no significant impact on BMD. In addition to BMD, bone markers such as serum osteocalcin, urinary deoxypyridinoline, and tartrate-resistant acid phosphatase have been evaluated to elucidate the mechanistic effects of soy isoflavones on bone metabolism. These markers provide insights into bone turnover, resorption, and formation. Clinical trials have reported mixed findings regarding the influence of soy isoflavones on bone markers, reflecting the complexity of their interaction with bone physiology

Phytochemicals and Glioma: Results from Dietary Mixed Exposure

The information about phytochemicals’ potential to prevent cancer is encouraging, including for glioma. However, most studies on phytochemicals and glioma mainly focused on preclinical studies. Their epidemiological studies were not sufficient, and the evidence on the dose–response relationship is usually limited. Therefore, this investigation examined the association between dietary phytochemical intake and glioma in Chinese adults. This case–control study was carried out in a hospital in China. Based on the dietary information obtained from the food frequency questionnaire, the researchers estimated the phytochemical intake of 506 patients with glioma and 506 controls. Compared with participants in the lowest tertile, the highest intakes of carotene, flavonoids, soy isoflavones, anthocyanin, and resveratrol were associated with a reduced risk of glioma. The WQS and BKMR models suggested that anthocyanin and carotene have a greater influence on glioma. The significant nonlinear dose–response associations between dietary phytochemicals and glioma were suggested using the restricted cubic spline function. According to this study on phytochemicals and glioma, higher intakes of carotene, flavonoids, soy isoflavones, anthocyanins, and resveratrol are linked to a lower risk of glioma. So, we might not be able to ignore how phytochemicals affect gliomas.

Intake of soy products and soy isoflavones in relation to ovarian reserve

To investigate the association between intake of soy food and isoflavone with ovarian reserve. Previous studies suggest on the relationship between soy intake and human fertility are inconsistent. Some clinical studies suggest that soy and phytoestrogens may not be deleterious to reproduction and may even be beneficial in couples undergoing infertility treatment. However, no studies have evaluated the relationship between soy or isoflavone intake with markers of ovarian reserve other than follicle-stimulating hormone (FSH). Cross-sectional study. An academic fertility center. Patients presenting to an academic fertility center between 2007 and 2019 were invited to participate in the Environment and Reproductive Health Study. Six hundred and sixty seven participants reported their soy food intake and had an antral follicle count (AFC) assessment. Intake of 15 soy-based foods during the previous 3 months was obtained at baseline and intake of isoflavone was estimated. Participants were divided into 5 groups based on soy food and isoflavone intake considering those who did not consume soy as the reference group. Ovarian reserve was assessed using AFC as the primary outcome measure, with antimüllerian hormone (AMH) and FSH as secondary outcome measures. The AFC was measured on the third day of the menstrual cycle. Moreover, FSH and AMH levels were measured in blood samples obtained on the third day and the follicular phase of the menstrual cycle. To evaluate the association between soy intake and ovarian reserve, we used Poisson regression models for AFC and quantile regression models for AMH and day 3 FSH levels by adjusting for confounders. Participants had a median age of 35.0 years. The median intake of soy was 0.09 servings/day and isoflavones was 1.78 mg/day. Moreover, AFC, AMH, and FSH were unrelated to soy intake in crude analyses. We found no association between soy food intake with AFC or day 3 FSH level in multivariable models. However, participants in the highest category of soy food intake had significantly low AMH levels (-1.16, 95% confidence interval: -1.92, -0.41). Soy intake had no association with AFC, AMH, or FSH in sensitivity analyses that included using different cutoff points of soy intake, excluding participants in the highest 2.5 percentile of intake, and additional statistical adjustment for dietary patterns. The results of this study are not consistent with a strong positive or inverse association of soy or isoflavone intakes within the observed range of intake, which substantially overlaps with that in the general population of the United States as well as the ovarian reserve among individuals presenting to fertility centers.

Abstract P2-06-02: A randomized controlled trial of soy isoflavone intake on mammographic density among Malaysian women

Abstract Introduction: Soy intake is associated with lower breast cancer risk in observational studies of Asian women, but clinical trials of soy isoflavone (ISF) supplements report no effect on biomarkers of breast cancer risk among Caucasian women. To date, there are no such trials among Asian women living in Asia. We conducted a three-armed, randomized controlled trial (RCT) to assess the effects of one-year intervention of soy isoflavone supplements (100mg/day) or soy isoflavones through diet (50mg/day) on mammographic density (MD) change among peri- and postmenopausal Malaysian women. Methodology: Healthy women between 45-65 years old were enrolled between November 2018 and December 2019 at a private tertiary hospital in Malaysia. Women were randomly assigned into the 100mg/day ISF Supplement arm, 50mg/day ISF Diet arm, or Control arm. Dense area was assessed from digital mammograms conducted at enrolment and after 12 months. We compared absolute and relative change in dense area over the study period by study arm using Kruskal Wallis tests. Results: Of the 118 women who received the intervention, 91 women completed the study whilst 27 women (23%) were lost to follow up. After 12 months of intervention, women in the ISF Supplement arm observed a marginally larger decline in dense area (-1.3cm2), compared to women in the ISF Diet arm (-0.5cm2) and Control arm (-0.8cm2), but this difference was not statistically significant (p=0.479). Notably, these effects appear to be stronger and limited to women who enrolled within 5 years of menopause, where up to 6cm2 decline in MD was observed in the ISF Supplement arm, compared to &amp;lt; 1.0cm in the Control arm (p=0.131). Conclusion: This RCT demonstrates a possible causal association between soy ISF intake and lower breast cancer risk among Asian women, specifically around the time of menopause, but these findings will require confirmation in a larger trial. Citation Format: Nadia Rajaram, Beverley Yap, Mikael Eriksson, Shivaani Mariapun, Lee Mei Tan, Hamizah Saat, Evelyn Ho, Nur Aishah Mohd Taib, Geok Lin Khor, Cheng Har Yip, Weang Kee Ho, Per Hall, Soo Hwang Teo. A randomized controlled trial of soy isoflavone intake on mammographic density among Malaysian women [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-06-02.

Phytoestrogens and Breast Cancer: Should French Recommendations Evolve?

Breast cancer (BC) occurs less frequently in Asia, where there is high soy consumption. It has been hypothesized that soy isoflavones could be protective against BC recurrence and mortality. At the same time, health organizations in several countries have differing recommendations for soy consumption (soy foods or dietary supplements) in BC survivors. The objective of this review is to analyze the literature and to determine whether it is justified to advise avoiding soy in dietary supplements and/or food in women with a history of BC. We conducted a systematic literature search with the Medline/Pubmed and Web of Science databases. Only prospective cohort studies published since 2009 were retained. The endpoint of studies was BC recurrence and/or mortality, and the association with soy isoflavone intake was specifically targeted. Seven studies were included. None of these studies found statistically significant adverse effects of soy consumption on BC recurrence or mortality (specific or all-cause). Overall, only one study was not able to find beneficial effects of soy intake on BC patients. The other studies concluded that there were positive associations but in very variable ways. Two studies found a decrease in BC recurrence associated with a higher isoflavone intake only for post-menopausal women. The other four studies concluded that there were positive associations regardless of menopausal status. Four studies showed better results on women with hormonal-sensitive cancer and/or patients receiving hormonal treatment. Only one found a stronger association for patients with ER-negative BC. No adverse effects of soy isoflavones on BC mortality/recurrence were found. Soy isoflavones may exert beneficial effects. These results coincide with other recent works and suggest that soy isoflavone intake is safe for BC survivors. Thus, these data no longer seem to coincide with the French recommendations, which could then be brought to evolve. However, in order to confirm the current results, larger studies are needed.

Soy product intake and risk of incident disabling dementia: the JPHC Disabling Dementia Study

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

P-647 Intake of soy foods and soy isoflavones in relation to ovarian reserve among women presenting to a fertility center

Abstract Study question Are soy food and isoflavone intakes associated with ovarian reserve as measured by antral follicle count (AFC)? Summary answer Within the observed range of intake, soy food or isoflavone consumptions are not associated with AFC. What is known already Phytoestrogens are structurally similar to 17β-estradiol, and bind to ER-α and ER-β in vitro resulting in weak estrogenic activity. Previous work in ruminants, felines and rodents has shown that exposure to phytoestrogens can have major adverse impacts on reproduction. However, findings of studies in humans suggest that soy foods and soy phytoestrogens may not have major deleterious impacts on reproductive hormone levels or reproductive outcomes, and could even be beneficial in couples undergoing infertility treatment. Study design, size, duration Women presenting to a large academic fertility center between April 2007 and December 2019 were invited to participate in the Environment and Reproductive Health (EARTH) Study, a prospective cohort study. Intake of 15 soy-based foods during the previous three months was obtained at baseline and intake of soy phytoestrogens was estimated from these reports. AFC was assessed with transvaginal ultrasound performed as part of diagnostic evaluation for infertility. Participants/materials, setting, methods We included 667 women who reported their soy food intake and had an AFC assessment. Women were divided in groups of increasing soy food and soy isoflavone intake with women who reported not consuming soy-based foods serving as the reference group. We evaluated the association of soy foods and soy isoflavones intake with AFC using Poisson regression models adjusting for confounders. Analyses were also stratified by age, BMI, and smoking status. Main results and the role of chance Women had median baseline age of 35.0 years and BMI of 23.4 kg/m2. Mean (range) intake of soy foods was 0.1 (0-7.4) servings/day, and mean (range) intake of isoflavones was 6 (0-166) mg/day, which is comparable to that of women in the general population of the USA. Intakes of soy foods or isoflavones were not related to AFC. The median (IQR) AFC for women who did not consume soy foods and women in the highest category of soy intake (&amp;gt;0.45 servings/day, median 0.88 servings/day) were 12 (9, 18) and 13 (9, 19). After adjustment for potential confounders, the mean difference in AFC between women in the highest category of soy intake and women who did not consume soy was -0.5% (-6.6%, 6.1%). Soy food intake remained unrelated to AFC when intake was categorized using different cutoff values when intake was modeled as a continuous variable when departures from a linear association were considered, and when we excluded from analysis 76 women whose AFC ultrasound scan was performed before they completed the diet assessment. Soy intake was also unrelated to AFC within categories of age, BMI and smoking status. Findings for soy isoflavones mirrored those for soy-food intake. Limitations, reasons for caution Self-reported soy intake may have resulted in measurement error leading to attenuation of observed relations towards the null. Also, all participants were women presenting to a fertility center and therefore, findings may not be generalizable to women in the general population. Wider implications of the findings Our findings suggest soy food and isoflavone intakes within the ranges observed among women in the general population of the USA is unlikely to influence ovarian reserve in any meaningful way. Trial registration number Not applicable

Effects of Soy Isoflavones and Green Tea Extract on Simvastatin Pharmacokinetics and Influence of the SLCO1B1 521T > C Polymorphism.

ObjectivesGreen tea and soy products are extensively consumed by many people and they may influence the activity of drug metabolizing enzymes and drug transporters to result in drug interactions. This study was performed to evaluate the effect of green tea and soy isoflavone extracts on the pharmacokinetics of simvastatin in healthy subjects and to clarify the role of polymorphisms in the SLCO1B1 drug transporter in this effect.MethodsThis was an open-label, three-phase randomized crossover pharmacokinetic study. A single dose of simvastatin 20 mg was taken on three occasions (without herbs, with green tea, and with soy isoflavones) by healthy male Chinese subjects. The green tea and soy isoflavone extracts were given at a dose containing EGCG 800 mg once daily or soy isoflavones about 80 mg once daily for 14 days before simvastatin dosing with at least 4-weeks washout period between phases.ResultsAll the 18 subjects completed the study. Intake of soy isoflavones was associated with reduced systemic exposure to simvastatin acid [geometric mean (% coefficient of variation) AUC0–24h from 16.1 (44.2) h⋅μg/L to 12.1 (54.6) h⋅μg/L, P < 0.05) but not the lactone. Further analysis showed that the interaction between simvastatin and the soy isoflavones only resulted in a significant reduction of AUC in subjects with the SLCO1B1 521TT genotype and not in those with the 521C variant allele. There was no overall effect of the green tea extract on simvastatin pharmacokinetics but the group with the SLCO1B1 521TT genotype showed reduced AUC values for simvastatin acid.ConclusionThis study showed repeated administration of soy isoflavones reduced the systemic bioavailability of simvastatin in healthy volunteers that was dependent on the SLCO1B1 genotype which suggested that soy isoflavones-simvastatin interaction is impacted by genotype-related function of this liver uptake transporter.

Effect of soy isoflavones on C-reactive protein in chronic inflammatory disorders.

New evidence suggests that soy products might reduce chronic systemic inflammation. Therefore, we aimed to summarize the effect of soy isoflavones on serum concentration of C-reactive protein (CRP) among participants with chronic inflammatory disorders by conducting this study. Cochrane Library, Scopus, ISI Web of Science, clinicaltrials.gov, and PubMed were searched to identify randomized clinical trials (RCTs) published up to December 2020. The effect size was calculated by the mean change from baseline in concentrations of CRP and its standard deviation for both intervention and comparison groups. DerSimonian and Laird random-effects model was used when the heterogeneity test was statistically significant. In total, thirteen RCTs involving 1213 participants and ten RCTs involving 1052 participants were eligible for our systematic review and meta-analysis respectively. Study duration ranged from 4 to 96 weeks and soy isoflavones dose varied from 33 to 132 mg/day. Overall effect size indicated a non-significant effect on serum concentration of CRP following soy isoflavones intake (weighted mean differences (WMD)=-0.15 mg/L, 95% confidence interval (CI): -0.54, 0.23; p=0.430). Subgroup analysis revealed that soy isoflavones significantly reduced serum concentration of CRP in studies among participants with age >57 years and baseline CRP levels >3.75 mg/L. The present study proposed that soy isoflavones could not significantly reduce serum CRP levels. It seems more RCTs on participants with age more than 57 years and higher levels of CRP is necessary.

Mechanism of Soy Isoflavone Daidzein-Induced Female-Specific Anorectic Effect.

Epidemiological studies suggest that regular intake of soy isoflavone exerts a preventive effect on postmenopausal obesity and other forms of dysmetabolism. Estrogens inhibit eating behavior. Soy isoflavones may act as estrogen agonist in estrogen-depleted conditions, whereas they may either act as an estrogen antagonist or be ineffective in estrogen-repleted conditions. We investigated the effects of dietary soy isoflavone on food intake under various estrogen conditions using male, ovariectomized (OVX), and non-OVX female rats, and compared the effects with those of estradiol. We found that soy isoflavones reduced food intake in females specifically, regardless of whether ovariectomy had been performed, whereas subcutaneous implantation of estradiol pellet did not reduce food intake in intact female rats, but did so in OVX female and male rats. Contrary to this hypothesis, the reduction in food intake may not be caused by the estrogenic properties of soy isoflavones. It is of great interest to understand the mechanisms underlying the anorectic effects of soy isoflavones. In this non-systematic review, we summarize our recent studies that have investigated the bioactive substances of anorectic action, pharmacokinetic properties of soy isoflavones, and the modification of central and peripheral signals regulating appetite by soy isoflavones, and selected studies that were identified via database mining.

Associations of dietary intakes of calcium, magnesium and soy isoflavones with osteoporotic fracture risk in postmenopausal women: a prospective study.

The role of dietary factors in osteoporotic fractures (OFs) in women is not fully elucidated. We investigated the associations between incidence of OF and dietary calcium, magnesium and soy isoflavone intake in a longitudinal study of 48 584 postmenopausal women. Multivariable Cox regression was applied to derive hazard ratios (HRs) and 95 % confidence intervals (CIs) to evaluate associations between dietary intake, based on the averages of two assessments that took place with a median interval of 2⋅4 years, and fracture risk. The average age of study participants is 61⋅4 years (range 43⋅3-76⋅7 years) at study entry. During a median follow-up of 10⋅1 years, 4⋅3 % participants experienced OF. Compared with daily calcium intake ≤400 mg/d, higher calcium intake (>400 mg/d) was significantly associated with about a 40-50 % reduction of OF risk among women with a calcium/magnesium (Ca/Mg) intake ratio ≥1⋅7. Among women with prior fracture history, high soy isoflavone intake was associated with reduced OF risk; the HR was 0⋅72 (95 % CI 0⋅55, 0⋅93) for the highest (>42⋅0 mg/d) v. lowest (<18⋅7 mg/d) quartile intake. This inverse association was more evident among recently menopausal women (<10 years). No significant association between magnesium intake and OF risk was observed. Our findings provide novel information suggesting that the association of OF risk with dietary calcium intake was modified by Ca/Mg ratio, and soy isoflavone intake was modified by history of fractures and time since menopause. Our findings, if confirmed, can help to guide further dietary intervention strategies for OF prevention.

Isoflavones in Soybean as a Daily Nutrient: The Mechanisms of Action and How They Alter the Pharmacokinetics of Drugs.

Soybeans [Glycine max (L.)] are a good source of isoflavones. The main isoflavone components of soybean are daidzein, genistein, and glycitein. World soybean production is very high. Because of its pharmacological activity, soy isoflavone intake over a long period of time may result in interactions with the drugs. This review summarizes soy isoflavone-drug interactions based on the pharmacokinetic parameters. Soy isoflavones have pharmacokinetic interactions with celecoxib, theophylline, paclitaxel, midazolam, imatinib, carbamazepine, valproic acid, repaglinide, omeprazole and danofloxacin. This is due to the changes in the area under the curve, maximum serum concentration, time that a drug is present at the maximum concentration in serum, clearance and half-life of the drugs when delivered together with soy isoflavones. The mechanisms of pharmacokinetic interactions occurs through the inhibition/induction of drug metabolizing cytochrome P450 (CYP450) enzymes such as CYP3A4, CYP2A1, and CYP2C9 or through the inhibition of drug transporters such as P-glycoprotein and breast cancer resistance protein. Thus, the consumption of soybean, soy isoflavones or soy products with drugs needs to be reconsidered.

Associations of Dietary Intakes of Calcium, Magnesium, and Soy Isoflavones With Bone Fracture Risk in Men: A Prospective Study.

ABSTRACTThe role of dietary factors in osteoporotic fractures in men is underinvestigated. We examined the associations of dietary intakes of calcium, magnesium, and soy isoflavones with risk of osteoporotic fractures in the Shanghai Men's Health Study. Included in this prospective study were 61,025 men aged 40 to 74 years at study enrollment (2002–2006). The cohort was followed up via in‐person surveys for occurrence of bone fractures, major diseases, and survival status. Multivariable Cox regression was applied to evaluate the associations of variables under study (ie, dietary intakes of calcium, magnesium, and soy isoflavones) with incidence of osteoporotic and non‐osteoporotic fractures, measured by hazard ratio (HR) and 95% confidence interval (CI). During a median follow‐up of 9.5 years, 1.2% and 3.4% of participants experienced osteoporotic or non‐osteoporotic fractures, respectively. Dietary calcium intake was inversely associated with risk of osteoporotic fractures with adjusted HRs of 0.78 (95% CI 0.60–1.02) and 0.27 (95% CI 0.13–0.56), respectively, for intake levels of 401 mg/d and >1000 mg/d versus ≤400 mg/d. Higher magnesium intake was associated with increased risk of osteoporotic fractures after adjusting for dietary calcium intake, with HRs of 1.27 (95% CI 0.97–1.66) and 2.21 (95% CI 1.08–4.50), respectively, for intakes of 251 mg/d and >450 mg/d versus intake ≤250 mg/d. High soy isoflavone intake was associated with a 25% reduction of osteoporotic fracture risk (HR = 0.73, 95% CI 0.56–0.97 for soy isoflavone intake >45.2 mg/d versus <21.7 mg/d). Dietary intakes of calcium, magnesium, or soy isoflavones were unrelated to the risk of non‐osteoporotic fractures. Our study added to the evidence that dietary calcium intake was inversely associated with a reduced risk of osteoporotic fractures in a dose–response fashion, while high magnesium intake was associated with an increased risk. Our study also revealed a novel association between higher soy isoflavone consumption and osteoporotic fractures in men. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Advances in asthma: New understandings of asthma’s natural history, risk factors, underlying mechanisms, and clinical management

The last 2 years yielded a proliferation of high-quality asthma research. These include new understandings of the incidence and natural history of asthma, findings on the effects of exposure to air pollution, allergens, and intake of acetaminophen, soy isoflavones, and polyunsaturated fatty acids, and exposure to microbial products. The past 2 years have benefited from great strides in determining potential mechanisms of asthma development and asthma exacerbations. These novel understandings led to identification and development of exciting new avenues for potential therapeutic intervention. Finally, there has been significant progress made in the development of tools to facilitate the diagnosis of asthma and measurement of airway physiology and in precision diagnostic approaches. Asthma guidelines were updated and new insights into the pharmacologic management of patients, including biologics, were reported. We review the most notable advances in the natural history of asthma, risk factors for the development of asthma, underlying mechanisms, diagnostic approaches, and treatments. Although greater knowledge of the mechanisms underlying responses and nonresponses to novel therapeutics and across asthma phenotypes would be beneficial, the progress over just the past 2 years has been immense and impactful.