Measurement of bile acid production in hyperlipidemic man: does phenotype or methodology make the difference?

Bile acid production has been measured in 13 studies in 10 hyperlipidemic subjects by simultaneous use of isotope dilution kinetics and chemical balance methodology. When the data of all 13 studies were averaged, the correlation between the two sets of values was negative and weak (r - 0.01, NS). However, when the correlations for normoglyceridemic and hyperglyceridemic subjects were examined separately, a strong positive correlation was found between the values obtained by the two methods in normoglyceridemic subjects (r + 0.92, P less than 0.01) but not in hyperglyceridemic subjects (r - 0.25, NS). Examination of bile acid specific activity decay characteristics in eight studies, where bile was sampled up to six times within the first 24 hr after radio-labeled bile acid infusion, revealed differences in three rate of attainment of peak specific activity and in the time taken subsequently to achieve first order kinetic decay. However, analysis of the data from these eight studies by input-output analysis yielded values for primary bile acid synthesis no different that those generated by conventional isotope dilution kinetics. Thus, bile acid production in normoglyceridemic subjects may be accurately quantitated by either isotope dilution or chemical balance methodology. Our data, as well as results from other laboratories, indicate that the values obtained are strictly comparable. On the other hand, the quantitation of bile acid production in hyperglyceridemic subjects by isotope dilution kinetics gives higher values than those obtained by chemical balance methodology, and in addition, higher values than those obtained in patients with normal plasma triglyceride levels.