Effect of soy isoflavone supplementation on nitric oxide metabolism and blood pressure in menopausal women

Abstract

Background: Isoflavones, having chemical structures similar to estrogens, are believed to stimulate nitric oxide production and thus lower blood pressure. The efficacy of soy isoflavone supplementation to stimulate nitric oxide production and lower blood pressure in menopausal women with high normal blood pressure remains unknown.

Objective: The objective was to test the effect of soy isoflavone supplementation on nitric oxide production and blood pressure in menopausal women with high normal blood pressure.

Design: A randomized, double-blind, parallel, placebo-controlled 6-wk trial was conducted to assess the effects of daily supplementation with 80 mg soy hypocotyl isoflavones (in aglycone units) on nitric oxide metabolism and blood pressure in 24 menopausal women with 12 women per group. Changes in nitric oxide metabolism were assessed via a primed, constant-infusion protocol with [15N]arginine and [13C]- and [2H]citrulline. Changes in blood pressure and associated vascular hemodynamics were assessed via office and 24-h ambulatory blood pressure monitoring, forearm blood flow, and indexes of arterial compliance.

Results: When compared with placebo and after control for pretreatment values, soy isoflavone supplementation had no effect on arginine flux, citrulline flux, nitric oxide synthesis, blood pressure, forearm blood flow, or estimates of arterial stiffness.

Conclusion: Daily supplementation with 80 mg soy hypocotyl isoflavones over a 6-wk period had no effect on nitric oxide metabolism or blood pressure and associated vascular hemodynamics in menopausal women with high normal blood pressure.

FIGURE 1.

Schematic diagram of the study design. At screening 1, informed consent was obtained from all potential study subjects followed by blood pressure and heart rate measurements. A fasting blood sample was collected for clinical blood chemistry, thyroid function, and follicle-stimulating hormone and isoflavone concentrations. At screening 2, study subjects who met the study inclusion criteria returned 1 wk later for a physical examination, dietary guidance to avoid foods high in nitrates, and blood pressure and heart rate measurements. The 2-d hemodynamic evaluation and stable-isotope infusion study were done on each subject at baseline and at the end of the 6-wk treatment period. The subjects were randomly assigned after the baseline assessments. All subjects continued to consume the placebo or isoflavone tablets until all posttreatment assessments had been done. Another fasting blood sample was collected at the end of the 6-wk treatment period to assess compliance.

FIGURE 2.

Natural logarithmic transformation of blood isoflavone concentrations in the placebo group and the soy isoflavone–supplemented group at the end of the 6-wk study period. The asterisks above the columns denote significant differences (P < 0.01) between the 2 groups. The error bar above each column represents SD.