title: Large inter-individual variation in isoflavone plasma concentration limits use of isoflavone intake data for risk assessment.
abstract: OBJECTIVE
  Isoflavones are present in soy foods and soy-based supplements. Despite low plasma isoflavone concentrations in the general Western population, concentrations in supplement users exceed those suggested to be beneficial for health in Asian populations, raising concerns for adverse effects. To aid risk assessment, quantification of the relation between isoflavone intake and plasma concentrations is essential.
  
  
  METHODS
  Plasma samples were collected from postmenopausal women in three placebo-controlled crossover studies with 8-week periods for supplements (two studies, ~100 mg isoflavones/day, n=88) or 4-week periods for soy foods (one study, ~48 mg isoflavones/day, n=15). Plasma isoflavone concentrations (daidzein, equol, genistein and glycitein) were quantified using high-performance liquid chromatography and electrochemical detection. The association between plasma concentrations and isoflavone intake, equol producer status, intake-producer interaction and background dietary intake was assessed based on the assumption of a log-linear relation.
  
  
  RESULTS
  Median plasma total isoflavone concentrations after the soy food and supplement interventions were respectively 2.16 and 3.47 μmol/l for equol producers and 1.30 and 2.39 μmol/l for non-producers. Regression analysis showed that doubling isoflavone intake increased plasma concentrations by 55-62% (±s.e. 1-2%, R(2)>0.87) for daidzein, genistein, equol (only for producers) and total isoflavones; for glycitein the association was weaker (15±1%, R(2)=0.48). Adjustments for energy, carbohydrate and fat intake did not affect these estimates. Inter-individual variation, estimated based on repeated measures in one of the studies, was 30-96%.
  
  
  CONCLUSIONS
  Although the relation between isoflavone intake and plasma concentrations was adequately quantified, the use of isoflavone intake data for risk assessment needs caution due to large inter-individual variation in plasma concentrations.
authors.affiliation: Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
authors.forename: V
authors.initials: V
authors.lastname: van der Velpen
authors.affiliation: 1] Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands [2] RIKILT, Wageningen University & Research Centre, Wageningen, The Netherlands.
authors.forename: P C
authors.initials: PC
authors.lastname: Hollman
authors.affiliation: Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: van Nielen
authors.affiliation: Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
authors.forename: E G
authors.initials: EG
authors.lastname: Schouten
authors.affiliation: Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Mensink
authors.affiliation: Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: Van't Veer
authors.affiliation: Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Geelen
mesh_terms: D000368:Aged; D044466:Asian People; D018592:Cross-Over Studies; D019587:Dietary Supplements / Q000706:statistics & numerical data; D060754:Equol / Q000008:administration & dosage / Q000097:blood; D005260:Female; D019833:Genistein / Q000008:administration & dosage / Q000097:blood; D006801:Humans; D007529:Isoflavones / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood*; D008875:Middle Aged; D017698:Postmenopause; D018570:Risk Assessment; D045730:Soy Foods / Q000706:statistics & numerical data
chemical_list: D007529:Isoflavones; D060754:Equol; C004742:daidzein; C086566:glycitein; D019833:Genistein