title: Acute benefits of the microbial-derived isoflavone metabolite equol on arterial stiffness in men prospectively recruited according to equol producer phenotype: a double-blind randomized controlled trial.
abstract: BACKGROUND
  There is much speculation with regard to the potential cardioprotective benefits of equol, a microbial-derived metabolite of the isoflavone daidzein, which is produced in the large intestine after soy intake in 30% of Western populations. Although cross-sectional and retrospective data support favorable associations between the equol producer (EP) phenotype and cardiometabolic health, few studies have prospectively recruited EPs to confirm this association.
  
  
  OBJECTIVE
  The aim was to determine whether the acute vascular benefits of isoflavones differ according to EP phenotype and subsequently investigate the effect of providing commercially produced S-(-)equol to non-EPs.
  
  
  METHODS
  We prospectively recruited male EPs and non-EPs (n = 14/group) at moderate cardiovascular risk into a double-blind, placebo-controlled crossover study to examine the acute effects of soy isoflavones (80-mg aglycone equivalents) on arterial stiffness [carotid-femoral pulse-wave velocity (cfPWV)], blood pressure, endothelial function (measured by using the EndoPAT 2000; Itamar Medical), and nitric oxide at baseline (0 h) and 6 and 24 h after intake. In a separate assessment, non-EPs consumed 40 mg S-(-)equol with identical vascular measurements performed 2 h after intake.
  
  
  RESULTS
  After soy intake, cfPWV significantly improved in EPs at 24 h (cfPWV change from 0 h: isoflavone, -0.2 ± 0.2 m/s; placebo, 0.6 ± 0.2 m/s; P < 0.01), which was significantly associated with plasma equol concentrations (R = -0.36, P = 0.01). No vascular effects were observed in EPs at 6 h or in non-EPs at any time point. Similarly, no benefit of commercially produced S-(-)equol was observed in non-EPs despite mean plasma equol concentrations reaching 3.2 μmol/L.
  
  
  CONCLUSIONS
  Acute soy intake improved cfPWV in EPs, equating to an 11-12% reduced risk of cardiovascular disease if sustained. However, a single dose of commercially produced equol had no cardiovascular benefits in non-EPs. These data suggest that the EP phenotype is critical in unlocking the vascular benefits of equol in men, and long-term trials should focus on confirming the implications of EP phenotype on cardiovascular health. This trial was registered at clinicaltrials.gov as NCT01530893.
authors: Department of Nutrition, Norwich Medical School, University of East Anglia, Norwich, United Kingdom.
authors: Sara
authors: S
authors: Hazim
authors: Department of Nutrition, Norwich Medical School, University of East Anglia, Norwich, United Kingdom.
authors: Peter J
authors: PJ
authors: Curtis
authors: Department of Nutrition, Norwich Medical School, University of East Anglia, Norwich, United Kingdom.
authors: Manuel Y
authors: MY
authors: Schär
authors: Department of Nutrition, Norwich Medical School, University of East Anglia, Norwich, United Kingdom.
authors: Luisa M
authors: LM
authors: Ostertag
authors: Department of Nutrition, Norwich Medical School, University of East Anglia, Norwich, United Kingdom.
authors: Colin D
authors: CD
authors: Kay
authors: Department of Nutrition, Norwich Medical School, University of East Anglia, Norwich, United Kingdom.
authors: Anne-Marie
authors: AM
authors: Minihane
authors: Department of Nutrition, Norwich Medical School, University of East Anglia, Norwich, United Kingdom a.cassidy@uea.ac.uk.
authors: Aedín
authors: A
authors: Cassidy
mesh_terms: D000368:Aged; D001419:Bacteria / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000097:blood / Q000503:physiopathology / Q000517:prevention & control; D018592:Cross-Over Studies; D003430:Cross-Sectional Studies; D019587:Dietary Supplements; D004311:Double-Blind Method; D060754:Equol / Q000096:biosynthesis / Q000097:blood / Q000494:pharmacology; D000069196:Gastrointestinal Microbiome; D006801:Humans; D007529:Isoflavones / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D048789:Phytoestrogens / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D008517:Phytotherapy; D010936:Plant Extracts / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D011446:Prospective Studies; D063177:Pulse Wave Analysis; D013025:Glycine max / Q000737:chemistry*; D059289:Vascular Stiffness / Q000187:drug effects* / Q000502:physiology
chemical_list: D007529:Isoflavones; D048789:Phytoestrogens; D010936:Plant Extracts; D060754:Equol; C004742:daidzein
keywords: CVD risk; arterial stiffness; equol producer phenotype; flavonoids; isoflavone; vascular function