Novel effects of phytoestrogenic soy isoflavones on serum calcium and chloride in premenopausal women: A 2-year double-blind, randomized, placebo-controlled study

Leejane Lu, Nai Wei Chen, Fatima Nayeem, V-M Ramanujam, Yong Fang Kuo, Donald G. Brunder, Manubai Nagamani, Karl Anderson

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Abstract

Background: Soy phytoestrogens are potential alternatives to postmenopausal hormone replacement therapy (HRT). Adverse effects of HRT such as myocardial infarction, stroke, and pulmonary embolism are mediated by calcium-induced signaling. Objective: To determine whether soy isoflavones affect serum calcium in healthy female subjects. Design: In a double-blind trial, 197 premenopausal women were randomly assigned to either isoflavone (N = 99) or placebo pills (N = 98) 5 days per week for up to 2 years, plus prenatal vitamins. Isoflavone pills contained 60 mg genistein, 60 mg daidzein and 16.6 mg glycitein (expressed as aglycone equivalents). All pills contained 15 mg riboflavin as an adherence marker. Blood chemistries and urinary daidzein, genistein and riboflavin were measured multiple times during the luteal phase before and during treatment. Results: Analysis of the adherent population (N = 83 per group), revealed significantly strong associations between urinary levels of isoflavones and serum concentrations of calcium (regression coefficients 0.082 for daidzein and 0.229 for genistein, all P < 0.01) and chloride (regression coefficient, -1.537 for genistein, P < 0.0001), mediated in part by albumin. The effects amounted to mean changes of +0.24 mg/dL for calcium and -1.45 mEq/L for chloride, with each visit for subjects excreting the most vs. the least amounts of isoflavones. These associations were not evident in the intention-to-treat analysis (N = 197) that did not assess expected variations in isoflavone levels within and between subjects from metabolism and adherence. Conclusions: These novel and strong effects of soy isoflavones on calcium homeostasis have important implications for long term effects of these natural substances on cardiovascular diseases.

Original languageEnglish (US)
JournalClinical Nutrition
DOIs
StateAccepted/In press - Jan 1 2017

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Calcium Chloride
Isoflavones
varespladib methyl
Placebos
Genistein
Serum
Calcium
Riboflavin
Chlorides
Phytoestrogens
Intention to Treat Analysis
Estrogen Replacement Therapy
Calcium Signaling
Luteal Phase
Hormone Replacement Therapy
Pulmonary Embolism
Vitamins
Albumins
Healthy Volunteers
Homeostasis

Keywords

  • Albumin
  • Calcium
  • Chloride
  • Daidzein
  • Genistein
  • Phytoestrogens

ASJC Scopus subject areas

  • Nutrition and Dietetics
  • Critical Care and Intensive Care Medicine

Cite this

@article{316cfc6f67ff479bbe7a5315b7d40e43,
title = "Novel effects of phytoestrogenic soy isoflavones on serum calcium and chloride in premenopausal women: A 2-year double-blind, randomized, placebo-controlled study",
abstract = "Background: Soy phytoestrogens are potential alternatives to postmenopausal hormone replacement therapy (HRT). Adverse effects of HRT such as myocardial infarction, stroke, and pulmonary embolism are mediated by calcium-induced signaling. Objective: To determine whether soy isoflavones affect serum calcium in healthy female subjects. Design: In a double-blind trial, 197 premenopausal women were randomly assigned to either isoflavone (N = 99) or placebo pills (N = 98) 5 days per week for up to 2 years, plus prenatal vitamins. Isoflavone pills contained 60 mg genistein, 60 mg daidzein and 16.6 mg glycitein (expressed as aglycone equivalents). All pills contained 15 mg riboflavin as an adherence marker. Blood chemistries and urinary daidzein, genistein and riboflavin were measured multiple times during the luteal phase before and during treatment. Results: Analysis of the adherent population (N = 83 per group), revealed significantly strong associations between urinary levels of isoflavones and serum concentrations of calcium (regression coefficients 0.082 for daidzein and 0.229 for genistein, all P < 0.01) and chloride (regression coefficient, -1.537 for genistein, P < 0.0001), mediated in part by albumin. The effects amounted to mean changes of +0.24 mg/dL for calcium and -1.45 mEq/L for chloride, with each visit for subjects excreting the most vs. the least amounts of isoflavones. These associations were not evident in the intention-to-treat analysis (N = 197) that did not assess expected variations in isoflavone levels within and between subjects from metabolism and adherence. Conclusions: These novel and strong effects of soy isoflavones on calcium homeostasis have important implications for long term effects of these natural substances on cardiovascular diseases.",
keywords = "Albumin, Calcium, Chloride, Daidzein, Genistein, Phytoestrogens",
author = "Leejane Lu and Chen, {Nai Wei} and Fatima Nayeem and V-M Ramanujam and Kuo, {Yong Fang} and Brunder, {Donald G.} and Manubai Nagamani and Karl Anderson",
year = "2017",
month = "1",
day = "1",
doi = "10.1016/j.clnu.2017.11.002",
language = "English (US)",
journal = "Clinical Nutrition",
issn = "0261-5614",
publisher = "Churchill Livingstone",

}

TY - JOUR

T1 - Novel effects of phytoestrogenic soy isoflavones on serum calcium and chloride in premenopausal women

T2 - A 2-year double-blind, randomized, placebo-controlled study

AU - Lu, Leejane

AU - Chen, Nai Wei

AU - Nayeem, Fatima

AU - Ramanujam, V-M

AU - Kuo, Yong Fang

AU - Brunder, Donald G.

AU - Nagamani, Manubai

AU - Anderson, Karl

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Background: Soy phytoestrogens are potential alternatives to postmenopausal hormone replacement therapy (HRT). Adverse effects of HRT such as myocardial infarction, stroke, and pulmonary embolism are mediated by calcium-induced signaling. Objective: To determine whether soy isoflavones affect serum calcium in healthy female subjects. Design: In a double-blind trial, 197 premenopausal women were randomly assigned to either isoflavone (N = 99) or placebo pills (N = 98) 5 days per week for up to 2 years, plus prenatal vitamins. Isoflavone pills contained 60 mg genistein, 60 mg daidzein and 16.6 mg glycitein (expressed as aglycone equivalents). All pills contained 15 mg riboflavin as an adherence marker. Blood chemistries and urinary daidzein, genistein and riboflavin were measured multiple times during the luteal phase before and during treatment. Results: Analysis of the adherent population (N = 83 per group), revealed significantly strong associations between urinary levels of isoflavones and serum concentrations of calcium (regression coefficients 0.082 for daidzein and 0.229 for genistein, all P < 0.01) and chloride (regression coefficient, -1.537 for genistein, P < 0.0001), mediated in part by albumin. The effects amounted to mean changes of +0.24 mg/dL for calcium and -1.45 mEq/L for chloride, with each visit for subjects excreting the most vs. the least amounts of isoflavones. These associations were not evident in the intention-to-treat analysis (N = 197) that did not assess expected variations in isoflavone levels within and between subjects from metabolism and adherence. Conclusions: These novel and strong effects of soy isoflavones on calcium homeostasis have important implications for long term effects of these natural substances on cardiovascular diseases.

AB - Background: Soy phytoestrogens are potential alternatives to postmenopausal hormone replacement therapy (HRT). Adverse effects of HRT such as myocardial infarction, stroke, and pulmonary embolism are mediated by calcium-induced signaling. Objective: To determine whether soy isoflavones affect serum calcium in healthy female subjects. Design: In a double-blind trial, 197 premenopausal women were randomly assigned to either isoflavone (N = 99) or placebo pills (N = 98) 5 days per week for up to 2 years, plus prenatal vitamins. Isoflavone pills contained 60 mg genistein, 60 mg daidzein and 16.6 mg glycitein (expressed as aglycone equivalents). All pills contained 15 mg riboflavin as an adherence marker. Blood chemistries and urinary daidzein, genistein and riboflavin were measured multiple times during the luteal phase before and during treatment. Results: Analysis of the adherent population (N = 83 per group), revealed significantly strong associations between urinary levels of isoflavones and serum concentrations of calcium (regression coefficients 0.082 for daidzein and 0.229 for genistein, all P < 0.01) and chloride (regression coefficient, -1.537 for genistein, P < 0.0001), mediated in part by albumin. The effects amounted to mean changes of +0.24 mg/dL for calcium and -1.45 mEq/L for chloride, with each visit for subjects excreting the most vs. the least amounts of isoflavones. These associations were not evident in the intention-to-treat analysis (N = 197) that did not assess expected variations in isoflavone levels within and between subjects from metabolism and adherence. Conclusions: These novel and strong effects of soy isoflavones on calcium homeostasis have important implications for long term effects of these natural substances on cardiovascular diseases.

KW - Albumin

KW - Calcium

KW - Chloride

KW - Daidzein

KW - Genistein

KW - Phytoestrogens

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U2 - 10.1016/j.clnu.2017.11.002

DO - 10.1016/j.clnu.2017.11.002

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JF - Clinical Nutrition

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