Soy Isoflavones in Epidemiological Serum Samples: What are the Optimal Time Window and Concentration Cutoffs for Assignment of Equol Producer Status?

Background: The ability to produce equol from daidzein may explain observed inconsistencies in isoflavones’ health effects. Reliable identification of Equol Producers (EqPs) in non-clinical studies is limited by poor understanding of pharmacokinetics in producers and background concentrations in Equol Nonproducers (EqNPs). Objective: To characterize equol pharmacokinetics and identify optimal time windows and concentration cutoffs for assignment of EqP phenotype. Design: An optimal time window was identified using a pharmacokinetic study (N=10) with sampling every 2-3hrs for 24hrs following ingestion of 4mg daidzein. An optimal cut off was conducted through analysis of samples collected at baseline, 3 stages following 1 month intake of: (1) 38.5mg/day, (2) 77.0mg/day; (3) 115.4mg/day daidzein aglycone equivalents; and post onemonth washout period (N=7). Result: Serum equol peaked between 12-24 hrs following isoflavone intake. A 22nM threshold clearly distinguished between samples collected from EqPs and EqNPs 12-24 hours post-ingestion, while ratios of Equol/Daidzein did not. Following high isoflavone intake, no dose response in equol concentrations was observed in EqNPs. Conclusion: Serum equol concentrations greater than 22nM reliably indicate intestinal microflora ability to metabolize daidzein to Equol (EqP phenotype). Sampling 12-24hr post-ingestion maximizes equol producer status assignment accuracy.