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.Design: 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.
Highlights
There is growing interest in the cardioprotective role of the microbial-derived isoflavone metabolite equol, which is produced by 20–30% of Western [1] and 50–60% of Asian [2] populations after consumption of daidzein-rich soy foods
This has largely been stimulated by favorable associations in crosssectional analysis between the equol producer (EP)4 phenotype and established markers of vascular function, including blood pressure (BP) [3], arterial stiffness, and endothelial function [4] and, likewise, biomarkers relevant to vascular health including lipids [3, 5], inflammatory biomarkers, and nitric oxide (NO) [3, 6, 7]
In one of the first randomized controlled isoflavone trials to prospectively recruit EPs to our knowledge, we observed acute improvements in carotid-femoral pulse-wave velocity (cfPWV) after soy isoflavone intakes at a dose readily achieved through the habitual diet and provide evidence of the potential significant importance of the EP phenotype
Summary
There is growing interest in the cardioprotective role of the microbial-derived isoflavone metabolite equol, which is produced by 20–30% of Western [1] and 50–60% of Asian [2] populations after consumption of daidzein-rich soy foods This has largely been stimulated by favorable associations in crosssectional analysis between the equol producer (EP) phenotype and established markers of vascular function, including blood pressure (BP) [3], arterial stiffness, and endothelial function [4] and, likewise, biomarkers relevant to vascular health including lipids [3, 5], inflammatory biomarkers, and nitric oxide (NO) [3, 6, 7].
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