Iron deficiency enhances cholesterol gallstone formation

Sean M. Johnston, Kevin P. Murray, Scot A. Martin, Karen Fox-Talbot, Pamela A Lipsett, Keith D. Lillemoe, Henry A. Pitt

Research output: Contribution to journalArticle

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 7α-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.

Original languageEnglish (US)
Pages (from-to)354-362
Number of pages9
JournalSurgery
Volume122
Issue number2
DOIs
StatePublished - Aug 1997

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Gallstones
Iron
Cholesterol
Diet
Bile
Gallbladder
Liver
Enzymes
Sciuridae
Iron-Deficiency Anemias
Mixed Function Oxygenases

ASJC Scopus subject areas

  • Surgery

Cite this

Johnston, S. M., Murray, K. P., Martin, S. A., Fox-Talbot, K., Lipsett, P. A., Lillemoe, K. D., & Pitt, H. A. (1997). Iron deficiency enhances cholesterol gallstone formation. Surgery, 122(2), 354-362. https://doi.org/10.1016/S0039-6060(97)90027-1

Iron deficiency enhances cholesterol gallstone formation. / Johnston, Sean M.; Murray, Kevin P.; Martin, Scot A.; Fox-Talbot, Karen; Lipsett, Pamela A; Lillemoe, Keith D.; Pitt, Henry A.

In: Surgery, Vol. 122, No. 2, 08.1997, p. 354-362.

Research output: Contribution to journalArticle

Johnston, SM, Murray, KP, Martin, SA, Fox-Talbot, K, Lipsett, PA, Lillemoe, KD & Pitt, HA 1997, 'Iron deficiency enhances cholesterol gallstone formation', Surgery, vol. 122, no. 2, pp. 354-362. https://doi.org/10.1016/S0039-6060(97)90027-1
Johnston SM, Murray KP, Martin SA, Fox-Talbot K, Lipsett PA, Lillemoe KD et al. Iron deficiency enhances cholesterol gallstone formation. Surgery. 1997 Aug;122(2):354-362. https://doi.org/10.1016/S0039-6060(97)90027-1
Johnston, Sean M. ; Murray, Kevin P. ; Martin, Scot A. ; Fox-Talbot, Karen ; Lipsett, Pamela A ; Lillemoe, Keith D. ; Pitt, Henry A. / Iron deficiency enhances cholesterol gallstone formation. In: Surgery. 1997 ; Vol. 122, No. 2. pp. 354-362.
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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 7α-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.",
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T1 - Iron deficiency enhances cholesterol gallstone formation

AU - Johnston, Sean M.

AU - Murray, Kevin P.

AU - Martin, Scot A.

AU - Fox-Talbot, Karen

AU - Lipsett, Pamela A

AU - Lillemoe, Keith D.

AU - Pitt, Henry A.

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N2 - 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 7α-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.

AB - 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 7α-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.

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