Soy isoflavones (genistein, daidzein)

Soy isoflavones are polyphenolic phytoestrogens — plant-derived compounds structurally similar to 17β-estradiol — concentrated in soybeans and soy-derived foods, with genistein and daidzein as the two principal aglycones (bioactive forms after gut deglycosylation). Both bind preferentially to estrogen receptor beta (ERβ) with 100- to 1000-fold lower affinity than endogenous estrogen, producing tissue-selective partial agonist/antagonist effects. A relevant variable is equol production: approximately 20–30% of Western adults and 50–60% of Asian adults harbour bacteria (primarily Adlercreutzia equolifaciens and Slackia isoflavoniconvertens) that convert daidzein to S-equol, a metabolite with higher ERβ affinity, explaining much individual response variability. RCTs and meta-analyses support a significant reduction in hot-flash frequency (Luan 2025) and small LDL-cholesterol lowering (~5 mg/dL across 11 RCTs, Taku 2007); equol producers show greater benefit. A 2022 meta-analysis (Boutas et al., 18 studies) found no elevated breast cancer risk and a trend toward reduced recurrence, consistent with ERβ anti-proliferative signalling in mammary tissue — mechanistically distinct from ERα-driven tumour promotion by pharmaceutical oestrogens.