Relationship between the Serum Concentration of 7α-Hydroxycholesterol and Fecal Bile Acid Excretion in Humans

Abstract

Background: Serum levels of 7α-hydroxycholesterol have been shown to reflect the activity of cholesterol 7α-hydroxylase, the key enzyme of bile acid synthesis in the liver, but a comparison with direct measurements of bile acid synthesis rates has never been performed. Methods: 7α-Hydroxycholesterol was measured by gas-liquid chromatography/mass spectrometry and bile acid synthesis by the fecal balance method in 35 subjects. Results: A significant correlation was found between 7α-hydroxycholesterol concentration in serum and bile acid synthesis (r = 0.863, p < 0.001). Serum levels of 7α-hydroxycholesterol in 20 patients treated with a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor did not differ from levels obtained in healthy volunteers (78 ± 7 ng/ml versus 63 ± 5 ng/ml; NS). Treatment with fenofibrate reduced 7α-hydroxycholesterol concentrations in six patients from 107 ± 47 ng/ml to 61 ± 12 ng/ml (p < 0.05). Conclusions: We conclude that the concentration of 7α-hydroxycholesterol in serum is an indicator of bile acid synthesis and that serum levels of 7α-hydroxycholesterol are not affected in patients treated with HMG-CoA reductase inhibitors but are affected in those treated with fenofibrate.

Key Words:

• Bile acid synthesis
• cholesterol 7α-hydroxylase
• fenofibrate
• 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors
• mass spectrometry
• stable isotopes