title: The effect of soy phytoestrogen supplementation on thyroid status and cardiovascular risk markers in patients with subclinical hypothyroidism: a randomized, double-blind, crossover study.
abstract: BACKGROUND
  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.
  
  
  METHODS
  We conducted a randomized, double-blind, crossover study in a tertiary care setting.
  
  
  METHODS
  Sixty patients with subclinical hypothyroidism participated in the study.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Academic Endocrinology, Diabetes and Metabolism, Hull York Medical School, Hull HU3 2JZ, United Kingdom. thozhukat.sathyapalan@hyms.ac.uk
authors.forename: Thozhukat
authors.initials: T
authors.lastname: Sathyapalan
authors.forename: Alireza M
authors.initials: AM
authors.lastname: Manuchehri
authors.forename: Natalie J
authors.initials: NJ
authors.lastname: Thatcher
authors.forename: Alan S
authors.initials: AS
authors.lastname: Rigby
authors.forename: Tom
authors.initials: T
authors.lastname: Chapman
authors.forename: Eric S
authors.initials: ES
authors.lastname: Kilpatrick
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Atkin
mesh_terms: D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D018592:Cross-Over Studies; D019587:Dietary Supplements; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D007333:Insulin Resistance; D007529:Isoflavones / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D048789:Phytoestrogens / Q000737:chemistry / Q000494:pharmacology*; D012307:Risk Factors; D013025:Glycine max / Q000737:chemistry*; D013960:Thyroid Function Tests; D013961:Thyroid Gland / Q000187:drug effects*; D013974:Thyroxine / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D007529:Isoflavones; D008055:Lipids; D048789:Phytoestrogens; D002097:C-Reactive Protein; D013974:Thyroxine