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 < 0.05), and decreased diastolic blood pressure (DBP) (β-estimates: − 0.84 for DE, − 2.82 for GE, all P < 0.05) after controlling for calcium. The net intervention effects between the maximum and no isoflavone excretion were − 17.7 and + 13.8 mmHg changes of SBP, respectively, at serum calcium of 10.61 and 8.0 mg/dL, and about 2.6 mmHg decrease of DBP. Conclusions: Moderation by isoflavones of the physiological effect of calcium tends to normalize SBP, and this effect is most significant when calcium concentrations are at the upper and lower limits of the physiological norm. Isoflavones decrease DBP independent of calcium levels. Further studies are needed to assess the impact of this novel micronutrient effect on blood pressure homeostasis and cardiovascular health. Trial registration: www.clinicaltrials.gov identifier: NCT00204490.