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

Lee Jane W. Lu, Nai Wei Chen, Fatima Nayeem, Manubai Nagamani, Karl E. Anderson

Research output: Contribution to journalArticle

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 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.

Original languageEnglish (US)
JournalEuropean Journal of Nutrition
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Isoflavones
Homeostasis
Placebos
Blood Pressure
Calcium
Genistein
Micronutrients
Health

Keywords

  • Blood pressure homeostasis
  • Daidzein
  • Genistein
  • Micronutrients
  • Selective estrogen receptor modulator

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

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title = "Soy isoflavones interact with calcium and contribute to blood pressure homeostasis in women: a randomized, double-blind, placebo controlled trial",
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 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.",
keywords = "Blood pressure homeostasis, Daidzein, Genistein, Micronutrients, Selective estrogen receptor modulator",
author = "Lu, {Lee Jane W.} and Chen, {Nai Wei} and Fatima Nayeem and Manubai Nagamani and Anderson, {Karl E.}",
year = "2019",
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doi = "10.1007/s00394-019-02085-3",
language = "English (US)",
journal = "European Journal of Nutrition",
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T1 - Soy isoflavones interact with calcium and contribute to blood pressure homeostasis in women

T2 - a randomized, double-blind, placebo controlled trial

AU - Lu, Lee Jane W.

AU - Chen, Nai Wei

AU - Nayeem, Fatima

AU - Nagamani, Manubai

AU - Anderson, Karl E.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

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KW - Daidzein

KW - Genistein

KW - Micronutrients

KW - Selective estrogen receptor modulator

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