title: Iron deficiency enhances cholesterol gallstone formation.
abstract: BACKGROUND
  Cholesterol gallstones occur most commonly in multiparous women, but the causes for this phenomenon remain unclear. This same patient population is prone to chronic iron deficiency anemia. In addition, iron is known to play an important role in hepatic enzyme metabolism. Therefore, we tested the hypotheses that iron deficiency would alter hepatic cholesterol metabolism and enhance gallstone formation.
  
  
  METHODS
  Forty adult prairie dogs were fed either a control iron-supplemented (200 ppm), an iron-deficient (8 ppm), a 0.4% cholesterol iron-supplemented (200 ppm), or a 0.4% cholesterol iron-deficient (8 ppm) diet. After 8 weeks gallbladder bile, serum, and liver were harvested. Gallbladder bile was examined for cholesterol crystals and gallstones. Bile lipids and hepatic enzymes were measured, and a cholesterol saturation index (CSI) was calculated.
  
  
  RESULTS
  Animals receiving the iron-deficient diet were more likely to have cholesterol crystals in their bile than were animals on the control diet (80% vs. 20%; p < 0.05). Animals on the 0.4% cholesterol iron-deficient diet had more cholesterol crystals per high-powered field (79 +/- 10 vs. 49 +/- 9; p = 0.07), a higher molar % cholesterol (6.0 +/- 0.3 vs 4.4 +/- 0.5; p < 0.05), and a higher CSI (1.27 +/- 0.10 vs. 0.91 +/- 0.07; p < 0.05) compared to animals receiving the 0.4% cholesterol iron supplemented diet. The 7 alpha-hydroxylase levels were lower in the animals on the iron-deficient diet compared to those receiving the control diet (0.42 +/- 0.08 vs 1.17 +/- 0.40 pmol/mg per minute; p = 0.07).
  
  
  CONCLUSIONS
  These data suggest that an iron-deficient diet (1) alters hepatic enzyme metabolism, which, in turn, (2) increases gallbladder bile cholesterol and promotes cholesterol crystal formation. We conclude that iron deficiency plays a previously unrecognized role in the pathogenesis of cholesterol gallstone formation in women.
authors.affiliation: Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, Md., USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Johnston
authors.forename: K P
authors.initials: KP
authors.lastname: Murray
authors.forename: S A
authors.initials: SA
authors.lastname: Martin
authors.forename: K
authors.initials: K
authors.lastname: Fox-Talbot
authors.forename: P A
authors.initials: PA
authors.lastname: Lipsett
authors.forename: K D
authors.initials: KD
authors.lastname: Lillemoe
authors.forename: H A
authors.initials: HA
authors.lastname: Pitt
mesh_terms: D000818:Animals; D001646:Bile / Q000737:chemistry* / Q000187:drug effects; D002769:Cholelithiasis / Q000737:chemistry* / Q000209:etiology / Q000503:physiopathology*; D002784:Cholesterol / Q000032:analysis* / Q000097:blood; D002790:Cholesterol 7-alpha-Hydroxylase / Q000032:analysis; D002791:Cholesterol, Dietary; D003460:Crystallization; D005260:Female; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000032:analysis; D007501:Iron / Q000494:pharmacology; D000090463:Iron Deficiencies; D008099:Liver / Q000737:chemistry; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D012589:Sciuridae
chemical_list: D002791:Cholesterol, Dietary; D002784:Cholesterol; D007501:Iron; D006903:Hydroxymethylglutaryl CoA Reductases; D002790:Cholesterol 7-alpha-Hydroxylase