Isoflavone biomarkers are inversely associated with atherosclerosis progression in adults: a prospective study

Am J Clin Nutr. 2021 Jul 1;114(1):203-213. doi: 10.1093/ajcn/nqab008.


Background: Many studies have examined associations between dietary isoflavones and atherosclerosis, but few used objective biomarkers.

Objectives: We examined the associations of isoflavone biomarkers (primary analyses) and equol production (secondary analyses) with the progression of carotid intima-media thickness (cIMT), and whether inflammation, systolic blood pressure (SBP), blood lipids, and sex hormone-binding globulin (SHBG) mediated these associations, in Chinese adults.

Methods: This 8.8-y prospective study included 2572 subjects (40-75 y old) from the GNHS (Guangzhou Nutrition and Health Study; 2008-2019). The concentrations of daidzein, genistein, and equol were assayed by an HPLC-tandem MS in serum (n = 2572) at baseline and in urine (n = 2220) at 3-y intervals. The cIMT of the common carotid artery (CCA) and bifurcation segment were measured by B-mode ultrasound every 3 y, and the progressions of cIMT ( ∆cIMT) were estimated using the regression method.

Results: Multivariable linear mixed-effects models (LMEMs) and ANCOVA revealed that subjects with higher serum isoflavones tended to have lower increases of CCA-cIMT. The mean ± SEM differences in 8.8-y ∆CCA-cIMT between extreme tertiles of serum isoflavones were -17.1 ± 8.4, -20.6 ± 8.3, and -23.3 ± 10.4 μm for daidzein, total isoflavone, and equol (P-trends < 0.05), respectively. LMEMs showed that the estimated yearly changes (95% CIs) (μm/y) in CCA-IMT were -2.0 (-3.8, -0.3), -1.9 (-3.6, -0.1), and -2.1 (-3.8, -0.3) in the highest (compared with the lowest) tertile of daidzein, genistein, and total isoflavones, respectively (P-interaction < 0.05). Path analyses indicated that the serum equol-atherosclerosis association was mediated by increased SHBG and decreased SBP. Similar beneficial associations were observed in the secondary analyses.

Conclusions: Serum isoflavones and equol exposure were associated with reduced cIMT progression, mediated by SHBG and SBP.

Keywords: atherosclerosis; biomarker; equol; isoflavone; prospective study.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Atherosclerosis / blood*
  • Atherosclerosis / pathology*
  • Biomarkers / blood
  • Blood Pressure
  • Carotid Intima-Media Thickness*
  • Diet*
  • Female
  • Humans
  • Isoflavones / blood*
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Prospective Studies
  • Sex Hormone-Binding Globulin / metabolism
  • Time Factors


  • Biomarkers
  • Isoflavones
  • Sex Hormone-Binding Globulin