B Angelin

Postprandial serum bile acids in healthy man. Evidence for differences in absorptive pattern between individual bile acids.

The serum concentrations of cholic acid (C), chenodeoxycholic acid (CD), and deoxycholic acid (D) before and after a standardised meal were determined in five healthy female subjects using a highly specific and accurate gas chromatographic-mass spectrometric technique. The C level rose significantly 60 minutes after the meal, reached a peak after 90 minutes, and had returned to the original level after 150 minutes. In contrast, the serum concentrations of CD and D displayed a significant rise by 30 minutes, reached a peak after 90 minutes, but had not returned to fasting levels after 150 minutes. The serum bile acid responses after a meal suggest that there is considerable absorption of dihydroxy bile acids in the proximal small intestine in man.

Apparent selective bile acid malabsorption as a consequence of ileal exclusion: effects on bile acid, cholesterol, and lipoprotein metabolism.

A new model has been developed to characterise the effect of a standardised ileal exclusion on bile acid, cholesterol, and lipoprotein metabolism in humans. Twelve patients treated by colectomy and ileostomy for ulcerative colitis were studied on two occasions: firstly with a conventional ileostomy and then three months afterwards with an ileal pouch operation with an ileoanal anastomosis and a protective loop ileostomy, excluding on average 95 cm of the distal ileum. The ileostomy contents were collected during 96 hours and the excretion of bile acids and cholesterol was determined using gas chromatography-mass spectrometry. Fasting blood and duodenal bile samples were collected on two consecutive days. After the exclusion of the distal ileum, both cholic and chenodeoxycholic acid excretion in the ileostomy effluent increased four to five times without any change in cholesterol excretion. Serum concentrations of lathosterol (a marker of cholesterol biosynthesis) and 7 alpha-hydroxycholesterol (a marker for bile acid biosynthesis) were increased several fold. Plasma concentrations of total VLDL triglycerides were also increased whereas the concentrations of total and LDL cholesterol, and apolipoprotein B were decreased. There were no changes in biliary lipid composition or cholesterol saturation of bile. The results show that the exclusion of about 95 cm of distal ileum causes malabsorption of bile acids but apparently not of cholesterol. The bile acid malabsorption leads to increased synthesis of both bile acids and cholesterol in the liver. It is suggested that bile acids can regulate cholesterol synthesis by a mechanism independent of the effect of bile acids on cholesterol absorption. The enhanced demand for cholesterol also leads to a decrease in plasma LDL cholesterol and apolipoprotein B concentrations. The malabsorption of bile acids did not affect biliary lipid composition or cholesterol saturations of VLDL triglycerides.

Nucleation time of gall bladder bile in gall stone patients: influence of bile acid treatment.

The time required for precipitation of cholesterol crystals (nucleation time, NT) was determined and related to the cholesterol saturation in gall bladder bile of gall stone free subjects (n = 11), patients with pigment stones (n = 3), and patients with cholesterol gall stones (n = 30) undergoing cholecystectomy. Seven of the gall stone patients had been treated with chenodeoxycholic acid (CDCA) and nine with ursodeoxycholic acid (UDCA), 15 mg/kg/day for three weeks before operation. NT was longer in gall stone free subjects (mean, 20 days), patients with pigment stones (14 days) and patients treated with CDCA (24 days) and UDCA (17 days) compared with untreated patients with cholesterol gall stones (1.5 days). In spite of low cholesterol saturation and prolonged NT, and in contrast to those treated with CDCA, four of the nine patients treated with UDCA had cholesterol crystals in their bile. These observations give further support to the concept that the mechanism for inducing gall stone dissolution may be different for CDCA and UDCA.