Hydroxycholesterols in serum from hypercholesterolaemic patients with and without bile acid sequestrant therapy.
To assess the effect of bile acid sequestrant therapy on bile acid precursors in plasma, we determined hydroxycholesterols in serum from patients with primary hypercholesterolaemia. Compared with a group of 5 male and 12 female patients without any lipid-lowering drug therapy, which has normal to slightly elevated 7 alpha-hydroxycholesterol, normal 7 beta-hydroxycholesterol and high normal to elevated 26-hydroxycholesterol levels, a group of 5 male and 9 female patients, using colestipol had higher 7 alpha-hydroxycholesterol without overlap, and higher 7 beta-hydroxycholesterol levels, but similar levels of 26-hydroxycholesterol. In the latter group, the ratio between 7 alpha-hydroxycholesterol and total cholesterol in serum was also higher without overlap. Both groups did not differ for age, body weight, body mass index and serum lipid levels. In the group of patients without lipid-lowering drug therapy, 7 alpha-hydroxycholesterol correlated positively with total and low-densitylipoprotein cholesterol, 7 beta-hydroxycholesterol negatively with body weight and body mass index, and 26-hydroxycholesterol positively with body weight. In both groups, 7 alpha-hydroxycholesterol correlated positively with 7 beta-hydroxycholesterol. These results suggest that (1) bile acid sequestrants enhance bile acid synthesis via the 7 alpha-hydroxylation but not via the 26-hydroxylation pathway, (2) serum 7 alpha-hydroxycholesterol level and the ratio between this hydroxycholesterol and total cholesterol in serum might be suitable parameters to check intake of bile acid sequestrants irrespective of dose, and (3) 7 beta-hydroxycholesterol is unlikely to be the result of cholesterol auto-oxidation in vitro.
Department of Endocrinology, University Hospital, Groningen, The Netherlands.
J J
JJ
van Doormaal
N
N
Smit
B J
BJ
Koopman
J C
JC
van der Molen
B G
BG
Wolthers
H
H
Doorenbos
D000328:Adult; D001647:Bile Acids and Salts / Q000097:blood*; D003084:Colestipol / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006888:Hydroxycholesterols / Q000097:blood*; D006937:Hypercholesterolemia / Q000097:blood* / Q000188:drug therapy; D007408:Intestinal Absorption; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D011073:Polyamines / Q000627:therapeutic use*
D001647:Bile Acids and Salts; D006888:Hydroxycholesterols; D008055:Lipids; D011073:Polyamines; D003084:Colestipol