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.
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.
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DOI：
10.3945/ajcn.115.125690
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发表时间：
2016-03
期刊：
影响因子：
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通讯作者：
Cassidy A
中科院分区：
文献类型：
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作者：
Hazim S;Curtis PJ;Schär MY;Ostertag LM;Kay CD;Minihane AM;Cassidy A
背景：关于雌马酚潜在的心脏保护作用有很多猜测，雌马酚是一种微生物衍生的异黄酮大豆苷元代谢物，30% 的西方人群摄入大豆后在大肠中产生雌马酚。尽管横断面和回顾性数据支持雌马酚产生者 (EP) 表型与心脏代谢健康之间的良好关联，但很少有研究前瞻性招募 EP 来证实这种关联。目的：目的是确定异黄酮的急性血管益处是否因 EP 表型而异，并随后研究向非 EP 提供商业生产的 S-(–) 牛尿酚的效果。设计：我们前瞻性地招募了中等心血管风险的男性 EP 和非 EP（n = 14/组）进行双盲、安慰剂对照交叉研究，以检查大豆异黄酮（80 毫克苷元当量）对动脉僵硬度 [颈动脉-股动脉脉搏波速度 (cfPWV)]、血压、内皮功能（使用 EndoPAT 2000 测量； Itamar Medical），以及摄入后基线（0 小时）和 6 小时和 24 小时的一氧化氮。在一项单独的评估中，非 EP 摄入了 40 毫克 S-(–) 牛马酚，并在摄入后 2 小时进行了相同的血管测量。结果：摄入大豆后，24 小时 EP 中的 cfPWV 显着改善（cfPWV 从 0 小时起的变化：异黄酮，-0.2 ± 0.2 m/s；安慰剂，0.6 ± 0.2 m/s；P < 0.01），这与血浆雌马酚浓度显着相关（R = -0.36，P = 0.01）。在 6 小时的 EP 中或在任何时间点的非 EP 中均未观察到血管效应。同样，尽管平均血浆雌马酚浓度达到 3.2 μmol/L，但商业生产的 S-(–) 牛马酚在非 EP 中没有观察到任何益处。结论：急性大豆摄入改善了 EP 的 cfPWV，如果持续的话，相当于心血管疾病风险降低 11-12%。然而，单剂量的商业生产的雌马酚对非 EP 没有心血管益处。这些数据表明，EP 表型对于释放雌马酚对男性的血管益处至关重要，长期试验应侧重于确认 EP 表型对心血管健康的影响。该试验在 ClinicalTrials.gov 上注册为 NCT01530893。
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.