title: Research protocol: effect of natural S-equol on blood pressure and vascular function--a six-month randomized controlled trial among equol non-producers of postmenopausal women with prehypertension or untreated stage 1 hypertension.
abstract: BACKGROUND
  Although higher habitual soy intake is associated with lower blood pressure (BP) and stroke incidence, clinical trials using soy protein or isoflavones on cardiovascular risks yielded inconsistent results. The discrepancies are hypothesized to be due to the individuals' intestinal bacterial capacity to metabolite isoflavones daidzein into equol. Animal and in vitro studies have revealed that equol has stronger estrogen-like and anti-oxidative activity than isoflavones and possesses natriuretic and vasorelaxant properties which may play an important role in the prevention of hypertension. However, no clinical trial has examined the effect of equol on BP. We thus propose a 24-week randomized controlled trial to test the effectiveness of natural S-equol on BP and vascular function among equol non-producers.
  
  
  METHODS
  This will be a 6-month double-blind, randomized, placebo-controlled trial among 207 non-equol producing postmenopausal women with prehypertension or early untreated hypertension. Eligible participants who have completed a 2-week run-in will be randomized to either one of the 3 groups: placebo group, low-equol group (10 mg/d) and high equol group (20 mg/d). The outcome measures will be conducted at baseline and at the end of the trial including 24 h ambulatory BP, endothelial function (by ultrasound determined brachial flow mediated dilation), arterial stiffness (by pulse wave analysis) and other cardiovascular risk factors (lipid profile, glycemic control and inflammatory biomarkers). Urinary isoflavones will be tested for compliance assessment. One way analysis of variance will be applied to compare the 6-month changes in ambulatory BP or parameters of vascular function among the 3 treatment groups.
  
  
  CONCLUSIONS
  This study will be performed in community subjects. If the antihypertensive effect of equol is proven, the provision of natural equol to those high risk adults who are unable to produce equol will have enormous public health implications for the primary and secondary prevention of hypertension and cardiovascular diseases on a population basis. The research efforts will also have significant implications for industry in the provision of suitable soy products for the prevention of hypertension and its related complications.
  
  
  BACKGROUND
  The trial was registered in ClinicalTrials.gov with identifier of NCT02515682 .
authors.affiliation: Division of Family Medicine and Primary Care, The Jockey Club School of Public Health and Primary Care, the Chinese University of Hong Kong, Hong Kong, SAR. liuzhaomin@cuhk.edu.hk.
authors.forename: Zhao-min
authors.initials: ZM
authors.lastname: Liu
authors.affiliation: Division of Epidemiology, The Jockey Club School of Public Health and Primary Care, the Chinese University of Hong Kong, Hong Kong, SAR.
authors.forename: Suzanne C
authors.initials: SC
authors.lastname: Ho
authors.affiliation: Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, PR China.
authors.forename: Yu-ming
authors.initials: YM
authors.lastname: Chen
authors.affiliation: School of Nursing, Faculty of Health and Social Science, the Hong Kong Polytechnic University, Hong Kong, SAR.
authors.forename: Yao Jie
authors.initials: YJ
authors.lastname: Xie
authors.affiliation: Department of Sport and Health, Guangzhou Sport University, Guangzhou, PR China. zhiguan1980@163.com.
authors.forename: Zhi-guan
authors.initials: ZG
authors.lastname: Huang
authors.affiliation: Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, PR China.
authors.forename: Wen-hua
authors.initials: WH
authors.lastname: Ling
mesh_terms: D000368:Aged; D001794:Blood Pressure / Q000187:drug effects*; D002985:Clinical Protocols; D004311:Double-Blind Method; D060754:Equol / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007529:Isoflavones / Q000378:metabolism*; D008875:Middle Aged; D045283:Natriuretic Agents / Q000494:pharmacology / Q000627:therapeutic use; D010641:Phenotype; D048789:Phytoestrogens / Q000378:metabolism; D010936:Plant Extracts / Q000378:metabolism; D017698:Postmenopause; D058246:Prehypertension / Q000188:drug therapy*; D012107:Research Design; D030262:Soybean Proteins / Q000737:chemistry*; D013025:Glycine max / Q000737:chemistry; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D007529:Isoflavones; D045283:Natriuretic Agents; D048789:Phytoestrogens; D010936:Plant Extracts; D030262:Soybean Proteins; D014665:Vasodilator Agents; D060754:Equol; C004742:daidzein