SERUM CONCENTRATION OF 7-ALPHA-HYDROXYCHOLESTEROL AS AN INDICATOR OF BILE-ACID SYNTHESIS IN HUMANS

The serum concentration of 7 alpha-hydroxycholesterol as an indicator of total bile acid synthesis was investigated under different experime ntal conditions in humans. 7 alpha-Hydroxycholesterol was measured by gas-liquid chromatography-mass spectrometry, using [H-2(7)]7 alpha-hyd roxycholesterol and/or 5 alpha-cholestane-3 beta,6 beta-diol as intern al standards, and bile acid synthesis was estimated by the fecal balan ce method. Intraindividual variation was small when the concentration of 7 alpha-hydroxycholesterol was determined twice in the same subject 2 days to 11 months apart (7.3 +/- 6.5%, n = 52). In patients with ad vanced cirrhosis of the liver (n = 22) 7 alpha-hydroxycholesterol was 3.4-fold lower (22 ng/ml +/- 8) compared to matched controls (75 ng/ml +/- 19). Administration of cholestyramine (4 g b.i.d.) for 14 days in creased 7 alpha-hydroxycholesterol concentration in five healthy volun teers from 40 +/- 11 ng/ml to 181 +/- 95 ng/ml (P = 0.02) and fecal ex cretion of acidic sterols from 254 +/- 60 mg/d to 1336 +/- 344 mg/d (P < 0.01). Although a significant correlation was found between 7 alpha -hydroxycholesterol in serum and bile acid synthesis in patients with hypercholesterolemia (r = 0.847, P ( 0.001, n = 17), it was impossible to accurately determine bile acid synthesis from the serum levels of 7 alpha-hydroxycholesterol. Thus, determination of 7 alpha-hydroxychol esterol concentrations in serum can be used to assess changes in bile acid synthesis rates over short and long term periods under various ex perimental conditions, but not to calculate bile acid synthesis correc tly.