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Bile acid sequestrants: mechanisms of action on bile acid and cholesterol metabolism

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Summary

Interruption of the enterohepatic circulation of bile acids by cholestyramine or colestipol influences the hepatic metabolism of cholesterol in many ways. The synthesis of bile acids is increased, as reflected by a several-fold increase in the activity of the cholesterol 7a hydroxylase, the rate-determining enzyme in bile acid synthesis. The increased metabolism of cholesterol to bile acids causes an enhanced demand of cholesterol in the hepatocytes, which respond with both new synthesis of cholesterol, as reflected in a several-fold increase of the HMG-CoA reductase activity, and increased expression of LDL receptors. As a consequence, the plasma level of LDL-cholesterol is lowered. The hepatic secretion rate of VLDL particles is increased. Cholestyramine therapy does not affect the output of biliary lipids or the cholesterol saturation of bile, indicating that treatment with bile acid sequestrants should not be associated with any increased risk of gallstone formation.

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Authors and Affiliations

  1. Department of Medicine, Karolinska Institutet at Huddinge University Hospital, S-14186, Huddinge, Sweden

    K. Einarsson, S. Ericsson, M. Rudling, D. Ståhlberg & B. Angelin

  2. Department of Surgery, Karolinska Institutet at Huddinge University Hospital, S-14186, Huddinge, Sweden

    S. Ewerth & E. Reihnér

Authors
  1. K. Einarsson
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  2. S. Ericsson
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  3. S. Ewerth
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  4. E. Reihnér
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  5. M. Rudling
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  6. D. Ståhlberg
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  7. B. Angelin
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Einarsson, K., Ericsson, S., Ewerth, S. et al. Bile acid sequestrants: mechanisms of action on bile acid and cholesterol metabolism. Eur J Clin Pharmacol 40 (Suppl 1), S53–S58 (1991). https://doi.org/10.1007/BF03216291

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