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Background: The number of people with cognitive impairment, including dementia, in the world is steadily increasing. Although the consumption of isoflavones and soy is associated with a reduced risk of cardiovascular disease, it might also be associated with cognitive impairment. The low number of studies investigating the association between soy/isoflavone intake and cognitive function warrant additional research., Methods: The Japan Public Health Center-based prospective (JPHC) Study is a large population-based cohort. Midlife dietary intake of soy and the isoflavone genistein was assessed on two occasions: in the years 1995 and 2000. In 2014-2015, 1,299 participants from Nagano prefecture completed a mental health screening. Of these, a total of 1,036 participants were included in analyses. Logistic regression was used to determine Odds Ratios (OR) and 95% Confidence Intervals (CI) for the association between midlife energy-adjusted genistein and soy food intake and cognitive impairment., Results: There were 392 cases of cognitive impairment (346 cases of MCI and 46 cases of dementia). Compared to the lowest dietary quartile of energy-adjusted genistein intake, the highest quartile was significantly associated with cognitive impairment (OR = 1.51; 95% CI, 1.02-2.24; P for trend = 0.03) in the final multivariable analysis., Conclusion: High midlife intake of the isoflavone genistein is associated with late-life cognitive impairment.

Objective: To explore the association between isoflavone intake in early pregnancy (the critical window of masculinisation) and hypospadias. Since oestrogen is likely to contribute to the differentiation of male external genitalia, dietary intake of isoflavone, which has a similar structure to human oestrogen, may be associated with the occurrence of hypospadias. However, there has been little evidence of this association., Materials and Methods: We used data of a nationwide birth cohort study, which recruited women as early in pregnancy as possible throughout Japan between 2011 and 2014. From the response to a self-administered food-frequency questionnaire, the daily intake of genistein (as a representative for isoflavone) was estimated. Information on hypospadias cases that were diagnosed until the first month after birth was obtained from medical records. Odds ratios (ORs) of hypospadias were estimated using a logistic regression model., Results: Among 41,578 mothers, who delivered singleton live male births, the median genistein intake was 15.3 mg/day, and a total of 51 cases of hypospadias were identified. Compared with mothers in the reference group (genistein intake 11th-89th percentiles), those in the low intake group (≤10th percentile) had an elevated risk of their sons having hypospadias (multivariable-adjusted OR = 2.8, 95% confidence interval = 1.4-5.8). Adverse or beneficial effects of genistein on hypospadias were not observed in the high intake group (≥90th percentile) (OR = 0.9, 95% confidence interval = 0.4-2.4)., Conclusion: Low maternal intake of isoflavone in early pregnancy was associated with an elevated risk of hypospadias., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

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., (©2018 American Association for Cancer Research.)

Objective: The estrogenicity of dietary soy may increase the risk of diseases, such as uterine leiomyoma and endometriosis, which originate from uterine tissue and are predominant indications for hysterectomy. We sought to determine whether soy product intake is associated with an increased risk of premenopausal hysterectomy., Design: Prospective cohort study., Setting: Takayama City, Gifu, Japan., Subjects: A cohort of 1172 female residents randomly selected from participants in the Takayama Study who were aged 35-54 and premenopausal at the time they entered the study in 1992., Measurements: Diet including soy product and isoflavone intake was assessed by a validated semiquantitative food frequency questionnaire at baseline. Information on the onset of menopause and hysterectomy were obtained by a follow-up mail questionnaire in 1998., Results: During the 6 y study period, 31 women underwent premenopausal hysterectomies. The second tertile of isoflavone intake was significantly associated with an decreased risk of premenopausal hysterectomy compared to the lowest tertile of intake after controlling for age and total energy (rate ratio=0.35, 95% confidence interval 0.13-0.97), although the dose-response relationship was not statistically significant., Conclusions: It is possible that soy product intake may be inversely associated with diagnoses leading to hysterectomy. Future studies focusing on specific diseases will be required to examine this possibility., Sponsorship: Grants from the Ministry of Education, Science, Sports and Culture, Japan.