Measurement of bile acid synthesis by three different methods in hypertriglyceridemic and control subjects

In hypertriglyceridemic subjects, bile acid synthesis measured by isotope dilution is consistently higher than synthesis measured by fecal acidic sterol output. To see which of these two measurements was the more accurate, we compared them to synthesis measured by release of 14CO2 from [26-14C]cholesterol. In 14 hypertriglyceridemic subjects, mean +/- SEM synthesis by the CO2 method was 1540 +/- 199 micromol/day, similar to values by fecal acidic sterol output (1660 +/- 295). Both were significantly lower than values by isotope dilution (2520 +/- 269, P = 0.0001 and 0.0015, respectively). In 12 normolipidemic controls, mean +/- SEM synthesis by the CO2 method was 1230 +/- 189 micromol/day, nearly identical to synthesis by fecal acidic sterols (1220 +/- 187). Both were somewhat less than synthesis by isotope dilution (1590 +/- 133), but in neither case were the differences statistically significant (P = 0.098 and 0.129, respectively). In 3 hypertriglyceridemic subjects, synthesis measured by the CO2 method increased by 42%, 44%, and 109% after 4 days of bile sampling, suggesting that the isotope dilution procedure actually stimulated synthesis. Fraction of bile acid not absorbed during daily enterohepatic cycling was 8.4 +/- 1.4% in the hypertriglyceridemic subjects compared to 4.9 +/- 0.8% in the normolipidemic controls (P = 0.037). We suggest that during sampling of bile for isotope dilution measurements, the terminal ileum is abruptly presented with a large bolus of unadulterated bile acid, both because of artificial stimulation of gallbladder contraction and return of surplus collected bile to the subject. In hypertriglyceridemia, because of an inefficient absorptive mechanism, this may result in unusual loss of bile acid with consequent stimulation of bile acid synthesis.