The effect of soy phytoestrogen supplementation on thyroid status and cardiovascular risk markers in patients with subclinical hypothyroidism: a randomized, double-blind, crossover study

J Clin Endocrinol Metab. 2011 May;96(5):1442-9. doi: 10.1210/jc.2010-2255. Epub 2011 Feb 16.

Abstract

Context: There is concern whether soy phytoestrogens may affect thyroid function. If true, soy phytoestrogens may be expected to have a greater impact in subjects with subclinical hypothyroidism.

Objective: The primary aim was to determine the effect of soy phytoestrogen supplementation on thyroid function, with a secondary aim of assessing the effects on cardiovascular risk indices in patients with subclinical hypothyroidism.

Design and setting: We conducted a randomized, double-blind, crossover study in a tertiary care setting.

Participants: Sixty patients with subclinical hypothyroidism participated in the study.

Intervention: Patients were randomly assigned to either low-dose phytoestrogen (30 g soy protein with 2 mg phytoestrogens, representative of a Western diet) or high-dose phytoestrogen (30 g soy protein with 16 mg phytoestrogens, representative of a vegetarian diet) supplementation for 8 wk, then crossed over after an 8-wk washout period.

Main outcome measures: The primary outcome was progression to overt hypothyroidism, with secondary outcome measures of blood pressure, insulin resistance, lipids, and highly sensitive C-reactive protein (hsCRP).

Results: Six female patients in the study progressed into overt hypothyroidism with a standardized rate ratio of 3.6 (95% confidence interval, 1.9, 6.2) after 16-mg phytoestrogen supplementation. Both systolic and diastolic blood pressure decreased with 16 mg phytoestrogens, whereas systolic pressure alone decreased with 2 mg phytoestrogens. Insulin resistance (homeostasis model assessment of insulin resistance, 3.5 ± 0.09 vs. 2.6 ± 0.08; P < 0.02) and hsCRP (4.9 ± 0.04 vs. 3.9 ± 0.03; P < 0.01) decreased with 16 mg phytoestrogens. Lipid profile remained unchanged.

Conclusion: There is a 3-fold increased risk of developing overt hypothyroidism with dietary supplementation of 16 mg soy phytoestrogens with subclinical hypothyroidism. However, 16-mg soy phytoestrogen supplementation significantly reduces the insulin resistance, hsCRP, and blood pressure in these patients.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Blood Pressure / drug effects
  • C-Reactive Protein / metabolism
  • Cardiovascular Diseases / epidemiology*
  • Cross-Over Studies
  • Dietary Supplements*
  • Disease Progression
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Humans
  • Hypothyroidism / complications
  • Hypothyroidism / drug therapy
  • Hypothyroidism / physiopathology*
  • Insulin Resistance
  • Isoflavones / blood
  • Lipids / blood
  • Male
  • Middle Aged
  • Phytoestrogens / chemistry
  • Phytoestrogens / pharmacology*
  • Risk Factors
  • Soybeans / chemistry*
  • Thyroid Function Tests
  • Thyroid Gland / drug effects*
  • Thyroxine / therapeutic use
  • Treatment Outcome

Substances

  • Isoflavones
  • Lipids
  • Phytoestrogens
  • C-Reactive Protein
  • Thyroxine

Associated data

  • ISRCTN/ISRCTN55827330