Converting Equol Nonproducers to Producers: A Systematic Review of Randomized Clinical Trials
Jiatong Li, Mengyi Li, Saied Aboushanab, Mark Ebeid, Rieko Hatanaka, Miho Iida, Masato Takase, Ian Jacobs, Arnur Gusmanov, Aya Hirata, Naoko Miyagawa, Naoki Nakaya, Daisuke Sugiyama, Curtis Tilves, Atsushi Hozawa, Xingnan Li, Noel T. Mueller, Panayiotis V. Benos, Akira SekikawaABSTRACT
Soy isoflavones have been associated with benefits for menopausal symptoms, cardiovascular health, and cognitive function, yet randomized clinical trials (RCTs) in Western countries have produced inconsistent results. A key factor may be equol, a metabolite of daidzein with stronger estrogenic and antioxidant effects, produced at lower rates in Western than in East Asian populations. This systematic review evaluates RCTs aimed at converting equol nonproducers to producers (CRD420251038428). We searched PubMed, Embase, and Web of Science for RCTs published between 1991 and 2025. Twelve RCTs ( n = 730, 85.5% female) met inclusion criteria. Interventions included soy isoflavones alone, soy with probiotics, fermented soy products, seaweed, and wheat bran. Studies were conducted in Japan ( n = 1), Brazil ( n = 1), and Western countries ( n = 10), with durations ranging from a single dose to 2.5 years. Study quality was assessed using the National Heart, Lung, and Blood Institute evaluation tool. None of the interventions significantly converted equol nonproducers into producers, with methodological limitations including small sample sizes, inconsistent equol measurement, and heterogeneous populations compromising reliability. Achieving equol producer status could unlock the full nutritional potential of soy isoflavones for menopausal, cardiovascular, and cognitive health. Future studies should prioritize standardized equol measurement, microbiome‐targeted interventions, and well‐powered, diverse populations to develop effective dietary strategies for Western populations where soy intake and equol production remain low.