Baseline arterial stiffness by equol producing status: The Arterial Stiffness Cognition, and Equol (ACE) Trial

Background: Arterial stiffness is commonly assessed by measuring the arterial pulse wave velocity (PWV), herein referred to as total PWV (T-PWV). The two components of T-PWV include structural PWV (S-PWV), caused by arterial remodeling, and load-dependent PWV (LD-PWV), caused by elevated blood pressure. Recent observations suggest that equol, a gut microbiome-derived metabolite of the soy-isoflavone may reduce T-PWV. Only 20-30% of Westerners possess the ability to convert daidzein to equol as compared to 50-70% of East Asians, thus equol supplementation may serve as a novel therapeutic approach. Clinical trials suggest that equol supplementation or soy isoflavone reduces T-PWV. However, it is not known whether T-PWV, S-PWV, or LD-PWV differ in equol producers vs. non-producers or if urinary equol is associated with these PWV measures. We leveraged baseline data from an ongoing clinical trial (Arterial Stiffness, Cognition, and Equol) to address this gap. We hypothesized that equol producers would have lower PWV measures compared to non-producers and that urinary equol concentration would be negatively associated with the PWV measures. Methods: The ACE enrolled 352 US adults with T-PWV data at baseline and low habitual soy consumption (Age=72 ± 5 years; Male/Female=49/51%; White/Black=79/21%; BMI=27.7 ± 4.6 kg/m^2). Prior to randomization, ACE participants were tested for equol producing status after a three-day soy loading challenge. An “equol producer” was defined as the urinary equol/daidzein ratio (log10 ≥ -1.75) after the three-day soy loading challenge. Arterial stiffness was assessed supine by measuring carotid-femoral T-PWV, with S-PWV and LD-PWV calculated using participant-specific exponential models that rely on concurrent blood pressure and T-PWV measures. Chi squared and Student’s Independent T-tests were used to compare categorical and continuous variables between equol producers and non-producers. ANCOVA models were used to determine whether equol producing status was associated with each PWV measure. Finally, generalized linear mixed models were used to assess whether the urinary equol/daidzein ratio was associated with each PWV measure. Models were adjusted for age, sex, race, education, BMI, smoking status, and alcohol use. Results: Approximately 30% of the baseline ACE cohort are equol producers. On average, equol producers had lower daidzein concentrations, diastolic blood pressure, and mean arterial pressure and higher equol concentrations (all p< 0.05). Contrary to our hypothesis, there was no difference in T-PWV or LD-PWV between equol producers and non-producers (all p >0.05). Further, equol producers had higher S-PWV compared to non-producers (equol producers=10.76 ± 2.11 vs. non-producer=10.27 ± 20.2, p=0.042). This difference persisted after covariate adjustments. Lastly, the urinary equol /daidzein ratio was associated with lower LD-PWV (β=-0.044, SE=0.022, P=0.043) and higher S-PWV (β=0.14, SE=0.068, P=0.039). Conclusions: Among people with habitual low soy intake, equol-producing status is associated with higher stiffness caused by structural remodeling, but lower stiffening caused by elevated blood pressure. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.