IRON-DEFICIENCY ENHANCES CHOLESTEROL GALLSTONE FORMATION

Background. Cholesterol gallstones occur most commonly in multiparous women, but the causes for this phenomenon remain unclear This same pat ient population is prone to chronic iron deficiency anemia. In additio n, iron is known to play an important role in hepatic enzyme metabolis m. Therefore, we tested the hypotheses that iron deficiency would alte r hepatic cholesterol metabolism and enhance gallstone formation. Meth ods. Forty adult prairie dogs were fed either a control iron-supplemen ted (200 ppm), an iron-deficient (8 ppm), a 0.4% cholesterol iron-supp lemented (200 ppm), or a 0.4% cholesterol iron-deficient (8 ppm) diet. lifter 8 weeks gallbladder bile, serum, and liver were harvested. Gal lbladder bile was examined for cholesterol crystals and gallstones. Bi le lipids and hepatic enzymes were measured, and a cholesterol saturat ion index (CSI) was calculated. Results. Animals receiving the iron-de ficient diet were more likely to have cholesterol crystals in their bi le than were animals on the control diet (80 % vs. 20 %; p < 0.05). An imals 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 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 receivi ng the 0.4% cholesterol iron supplemented diet. The 7 alpha-hydroxylas e 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 p mol/mg per minute p = 0.07). Conclusions. These data suggest that an i ron-deficient diet (1) alters hepatic enzyme,ne metabolism, which, in turn, (2) increases gallbladder bile cholesterol and promotes choleste rol crystal formation. We conclude that iron deficiency plays a previo usly unrecognized role in the pathogenesis of cholesterol gallstone fo rmation in women.