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

Sara Hazim, Peter J. Curtis, Manuel Y. Schär, Luisa M. Ostertag, Colin D Kay, Anne-Marie Minihane, Aedin Cassidy

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Background: There is much speculation regarding potential cardio-protective benefits of equol, a microbial-derived metabolite of the isoflavone daidzein, produced in the large intestine by 30% of Western populations following soy intake. Whilst cross-sectional and retrospective data support favorable associations between the equol producer (EP) phenotype and cardio-metabolic health, few studies have prospectively recruited EPs to confirm this.  Objective: To determine if the acute vascular benefits of isoflavones differ according to EP phenotypes and subsequently investigate the effect of providing commercially-produced S-(-) equol to non-EPs.  Design: We prospectively recruited male EPs and non-EPs (n=14 per group) at moderate cardiovascular (CV) risk to a double-blind, placebo controlled cross-over study to examine the acute effects of soy isoflavones (80 mg aglycone equivalents) on arterial stiffness (carotid to femoral pulse wave velocity (cfPWV)), blood pressure (BP), endothelial function (EndoPAT) and nitric oxide (NO), at baseline (0h), 6h, and 24h post intake. In a separate assessment, non-EPs consumed 40 mg S-(-) equol with identical vascular measurements performed 2 h following intake.  Results: Following soy intake, cfPWV was significantly improved in EPs at 24 h (cfPWV ∆ from 0 h; isoflavone -0.2±0.2, placebo 0.6±0.2; 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-EP’s at any time point. Similarly, no benefit of commercially produced S-(-)equol was observed in non-EPs despite mean plasma equol concentrations reaching 3.2µM.  Conclusions: Acute soy intake improved cfPWV in EPs, equating to a 11-12% reduced risk of CV disease if sustained. However, a single dose of commercially produced equol had no CV 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 CV health.
Original languageEnglish
Pages (from-to)694-702
Number of pages9
JournalThe American Journal of Clinical Nutrition
Issue number3
Early online date3 Feb 2016
Publication statusPublished - Mar 2016


  • CVD risk
  • isoflavone
  • flavonoids
  • vascular function
  • equol producer phenotype
  • arterial stiffness

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