Soy isoflavones interact with calcium and contribute to blood pressure homeostasis in women: a randomized, double-blind, placebo controlled trial

Background Estrogens and calcium regulate vascular health but caused adverse cardiovascular events in randomized trials. Objectives Whether phytoestrogenic soy isoflavones modulate the physiological effects of calcium on blood pressure was explored. Design A double-blind, randomized study assigned 99 premenopausal women to 136.6 mg isoflavones (as aglycone equivalents) and 98 to placebo for 5 days per week for up to 2 years. Blood pressure, serum calcium and urinary excretion of daidzein (DE) and genistein (GE) were measured repeatedly before and during treatment. Results Isoflavones did not affect blood pressure per intake dose assignment (i.e. intention-to-treat, n = 197), but significantly affected blood pressure per measured urinary excretion of isoflavones (i.e. per protocol analysis, n = 166). Isoflavones inversely moderated calcium effects on systolic blood pressure (SBP) (interaction term β -estimates: − 3.1 for DE, − 12.86 for GE, all P