Use of Fermented Red Clover Isoflavones in the Treatment of Overactive Bladder in Postmenopausal Women: A Randomized, Double-Blinded, Placebo-Controlled Trial

Postmenopausal women are at risk of developing an overactive bladder (OAB). Conventional vaginal estrogen has shown promise for symptom relief. Isoflavones have proven effective as an alternative to estrogen treatment against menopause-related symptoms. However, its effect on OAB symptoms has not been studied. This study investigates if fermented red clover isoflavones reduce OAB symptoms in postmenopausal women. In this randomized, double-blinded, placebo-controlled trial, women were administered red clover extract (RCE) or a placebo twice daily for three months. Women filled out the International Consultation on Incontinence Questionnaire Overactive Bladder (ICIQ-OAB) and Urinary Incontinence Short Form (ICIQ-UI-SF), together with a fluid intake and voiding diary. A total of 33 women (16 in the RCE group and 17 in the placebo group) were included in the analysis. Baseline demographics and OAB characteristics were comparable across groups. Intake of RCE did not lead to significant relief in most urinary bladder symptom measures, although a significant reduction in the bother of urinary urgency (p = 0.033) and a tendency towards a decreased ICIQ-OAB score were observed (p = 0.056). In contrast, the placebo exhibited a significant decrease in the ICIQ-OAB score (p = 0.021) and in some diary outcomes. We found that an intake of isoflavones did not relieve OAB symptoms in postmenopausal women.</p

GDF15 Provides an Endocrine Signal of Nutritional Stress in Mice and Humans.

GDF15 is an established biomarker of cellular stress. The fact that it signals via a specific hindbrain receptor, GFRAL, and that mice lacking GDF15 manifest diet-induced obesity suggest that GDF15 may play a physiological role in energy balance. We performed experiments in humans, mice, and cells to determine if and how nutritional perturbations modify GDF15 expression. Circulating GDF15 levels manifest very modest changes in response to moderate caloric surpluses or deficits in mice or humans, differentiating it from classical intestinally derived satiety hormones and leptin. However, GDF15 levels do increase following sustained high-fat feeding or dietary amino acid imbalance in mice. We demonstrate that GDF15 expression is regulated by the integrated stress response and is induced in selected tissues in mice in these settings. Finally, we show that pharmacological GDF15 administration to mice can trigger conditioned taste aversion, suggesting that GDF15 may induce an aversive response to nutritional stress.This work and authors were funded by the NIHR Cambridge Biomedical Research Centre; NIHR Rare Disease Translational Research Collaboration; Medical Research Council [MC_UU_12012/2 and MRC_MC_UU_12012/3]; MRC Metabolic Diseases Unit [MRC_MC_UU_12012/5 and MRC_MC_UU_12012.1]; Wellcome Trust Strategic Award [100574/Z/12/Z and 100140]; Wellcome Trust [107064 , 095515/Z/11/Z , 098497/Z/12/Z, 106262/Z/14/Z and 106263/Z/14/Z]; British Heart Foundation [RG/12/13/29853]; Addenbrooke’s Charitable Trust / Evelyn Trust Cambridge Clinical Research Fellowship [16-69] US Department of Agriculture: 2010-34323-21052; EFSD project grant and a Royal College of Surgeons Research Fellowship, Diabetes UK Harry Keen intermediate clinical fellowship (17/0005712). European Research Council, Bernard Wolfe Health Neuroscience Endowment, Experimental Medicine Training Initiative/AstraZeneca and Medimmune