title: Heme and non-heme iron consumption and risk of gallstone disease in men.
abstract: BACKGROUND
  Excessive iron intake can promote biliary cholesterol crystal formation in experimental studies. The absorption of heme iron is more complete than that of non-heme iron in humans; however, the effect of long-term consumption of heme and non-heme iron on the risk of gallstones is unknown.
  
  
  OBJECTIVE
  The objective of the study was to examine long-term iron intake in relation to the occurrence of gallstone disease.
  
  
  METHODS
  We prospectively studied intakes of heme and non-heme iron and the risk of gallstone disease in a cohort of 44 758 US men from 1986 to 2002. Iron consumption was assessed by using a validated semiquantitative food-frequency questionnaire. Newly diagnosed gallstone disease was ascertained biennially.
  
  
  RESULTS
  We documented 2468 incident cases of symptomatic gallstones during 597 699 person-years of follow-up. The age-adjusted relative risks (RRs) for men with intakes of heme iron and non-heme iron, when the highest and lowest quintiles were compared, were 1.21 (95% CI: 1.06, 1.37; P for trend = 0.0008) and 1.02 (95% CI: 0.90, 1.16; P for trend = 0.45), respectively. After adjustment for multiple potential confounding variables, when extreme quintiles were compared, the multivariate RR of heme iron intake was not significantly changed and remained significant with a dose-response relation (RR = 1.21; 95% CI: 1.03, 1.42; P for trend = 0.01), and that of non-heme iron intake was not significant (RR = 1.14; 95% CI: 0.99, 1.31; P for trend = 0.18).
  
  
  CONCLUSIONS
  Our findings suggest that a higher consumption of heme iron is associated with a greater risk of gallstone disease among men.
authors.affiliation: Division of Digestive Diseases and Nutrition, University of Kentucky Medical Center, Lexington, Kentucky 40536, USA. hpcjt@channing.harvard.edu
authors.forename: Chung-Jyi
authors.initials: CJ
authors.lastname: Tsai
authors.forename: Michael F
authors.initials: MF
authors.lastname: Leitzmann
authors.forename: Walter C
authors.initials: WC
authors.lastname: Willett
authors.forename: Edward L
authors.initials: EL
authors.lastname: Giovannucci
mesh_terms: D000328:Adult; D015331:Cohort Studies; D042882:Gallstones / Q000139:chemically induced / Q000453:epidemiology*; D006418:Heme / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D015994:Incidence; D007501:Iron / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D012306:Risk; D012307:Risk Factors; D011795:Surveys and Questionnaires
chemical_list: D006418:Heme; D007501:Iron