Lee-Jane W Lu1, Nai-Wei Chen2, Fatima Nayeem2, Manubai Nagamani3,4, Karl E Anderson5. 1. Department of Preventive Medicine and Community Health, The University of Texas Medical Branch, 700 Harborside Dr., Galveston, TX, 77555-1109, USA. llu@utmb.edu. 2. Department of Preventive Medicine and Community Health, The University of Texas Medical Branch, 700 Harborside Dr., Galveston, TX, 77555-1109, USA. 3. Department of Obstetrics and Gynecology, The University of Texas Medical Branch, 301 University Blvd, Galveston, TX, 77555, USA. 4. Houston Bay Area Fertility Center, Webster, TX, 77598, USA. 5. Department of Preventive Medicine and Community Health, The University of Texas Medical Branch, 700 Harborside Dr., Galveston, TX, 77555-1109, USA. kanderso@utmb.edu.
Abstract
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 toplacebo 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.
RCT Entities:
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.
Authors: JoAnn E Manson; Rowan T Chlebowski; Marcia L Stefanick; Aaron K Aragaki; Jacques E Rossouw; Ross L Prentice; Garnet Anderson; Barbara V Howard; Cynthia A Thomson; Andrea Z LaCroix; Jean Wactawski-Wende; Rebecca D Jackson; Marian Limacher; Karen L Margolis; Sylvia Wassertheil-Smoller; Shirley A Beresford; Jane A Cauley; Charles B Eaton; Margery Gass; Judith Hsia; Karen C Johnson; Charles Kooperberg; Lewis H Kuller; Cora E Lewis; Simin Liu; Lisa W Martin; Judith K Ockene; Mary Jo O'Sullivan; Lynda H Powell; Michael S Simon; Linda Van Horn; Mara Z Vitolins; Robert B Wallace Journal: JAMA Date: 2013-10-02 Impact factor: 56.272