Relationship between the serum concentration of 7 alpha-hydroxycholesterol and fecal bile acid excretion in humans.

BACKGROUND

Serum levels of 7 alpha-hydroxycholesterol have been shown to reflect the activity of cholesterol 7 alpha-hydroxylase, the key enzyme of bite acid synthesis in the liver, but a comparison with direct measurements of bile acid synthesis rates has never been performed.

METHODS

7 alpha-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 7 alpha-hydroxycholesterol concentration in serum and bile acid synthesis (r = 0.863, p < 0.001). Serum levels of 7 alpha-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 7 alpha-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 7 alpha-hydroxycholesterol in serum is an indicator of bile acid synthesis and that serum levels of 7 alpha-hydroxycholesterol are not affected in patients treated with HMG-CoA reductase inhibitors but are affected in those treated with fenofibrate.