Effect of Oral Chenodeoxycholic Acid on Bile Acid Kinetics and Biliary Lipid Composition in Women with Cholelithiasis

Danzinger, R. G.; Hofmann, Alan F.; Thistle, Johnson L.; Schoenfield, Leslie J.

doi:10.1172/jci107477

Cited by 200 publications

(55 citation statements)

References 33 publications

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“…In accordance with the results recorded for the normolipidemic controls in the present study, the synthesis of CD has been found to be about half that of C (9,20). Similar results concerning the ratio between the synthetic rates of the two primary bile acids were reported recently by Quarfordt and Greenfield (21), who studied the metabolic fate of [1-1H]cholesterol.…”

Section: Discussionsupporting

confidence: 92%

“…Several investigations with the isotope dilution technique have demonstrated that the pool size and synthesis of C in healthy subjects given diets of natural type average about 1,200 mg and 300 mg/day, respectively (8,9,17,19,20). In accordance with the results recorded for the normolipidemic controls in the present study, the synthesis of CD has been found to be about half that of C (9,20).…”

Section: Discussionmentioning

confidence: 99%

“…The present investigation is an extension of the previous one (3) and is aimed to characterize the bile acid kinetics in normolipidemic controls and in patients with four types of hyperlipoproteinemia under the same dietary conditions. Particular attention was paid to the possibility of sex differences and the effects of obesity and gallbladder disease known to influence the bile acid excretion (7) and the bile acid pool size (8)(9)(10), respectively.…”

Section: Introductionmentioning

confidence: 99%

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Bile Acid Kinetics in Relation to Sex, Serum Lipids, Body Weights, and Gallbladder Disease in Patients with Various Types of Hyperlipoproteinemia

Einarsson¹,

Hellström²,

Kallner³

1974

J. Clin. Invest.

122

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The total bile acid formation was within normal limits in patients with hyperlipoproteinemia types Ha and MIb. On the average the production of cholic acid (C) represented less than 50% of the total bile acid synthesis in both groups. The corresponding value recorded for the controls was 64±2% (mean±i-SEM). The synthesis of C in hyperlipoproteinemia type Ha was significantly below normal. Of the 27 patients with the type IV pattern, 18 had a synthesis of C and C + chenodeoxycholic acid (CD) that exceeded the upper range recorded for the controls. In these subjects the C formation represented 73±3% of the total bile acid synthesis. Similar findings were also encountered in the five patients with the type V lipoprotein pattern studied. The bile acid pool size of the 11 patients with hyperlipoproteinemia type IV, who had been cholecystectomized or suffered from cholelithiasis, was 900 mg smaller on the average than that of the other subjects with the same type of hyperlipoproteinemia. However, the pool size in the former subjects still tended to be higher than that of the control subjects without evidence of gallbladder "disease". In all groups of subjects the formation of bile acids tended to be higher in the male than in the female subjects. Bile acid synthesis showed no linear correlation to actual body weight, relative body weight, or body surface area. A moderate weight reduction in five patients (one with type IIb and four with type IV pattern) was followed by a 50% reduction of the C and CD synthesis.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Bile Acid Kinetics in Relation to Sex, Serum Lipids, Body Weights, and Gallbladder Disease in Patients with Various Types of Hyperlipoproteinemia

Einarsson¹,

Hellström²,

Kallner³

1974

J. Clin. Invest.

122

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“…Excess conjugation of bile acids may produce a low percentage of taurineconjugates in the biliary bile acid composition (Danzinger et al 1973;Hardison 1978). The administered UDCA, absorbed at a rate of about 90% in the intestine (Fedorowski et al 1977), demands the conjugation along with the endogenous bile acids, and may produce a high G/T ratio (Stiehl et al 1980; Kanazawa et al 1980).…”

Section: Discussionmentioning

confidence: 99%

“…Since the dissolution of cholesterol gallstones by chenodeoxycholic acid (CDCA) (Bell et al 1972;Danzinger et al 1972) and ursodeoxycholic acid (UDCA) (Sugata and Shimizu 1974;Makino et al 1975) was demonstrated, an attention has been focused on the metabolism of bile acids in man in connection with the dissolution effect ; Tokyo Cooperative Gallstone Study Group 1980) and its mechanism (Admirand and Small 1968;Danzinger et al 1973;Fedorowski et al 1977;Carey and Small 1978;Stiel et al 1978Stiel et al , 1980. Current methods for the determination of bile acids involve alkaline hydrolysis of the conjugates under drastic conditions followed by gas-liquid chromatographic (GLC) separation of liberated bile acids (Nakayama 1967;Iwabuchi 1978).…”

mentioning

confidence: 99%

The effect of ursodeoxycholic acid on biliary bile acid composition in patients with cholesterol gallstone.

Kanazawa

Koizumi

Hirakawa

et al. 1982

Tohoku J. Exp. Med.

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To elucidate the role of conjugated biliary bile acids in gallstone dissolution, the acids in bile were determined by high-performance liquid chromatography before and after the treatment with ursodeoxycholic acid for 3-26 months in patients with gallstone. The stone-dissolving effect of ursodeoxycholic acid was confirmed in 7 of 10 patients and the lithogenic index lowed significantly after the treatment.The compositions of cholate, chenodeoxycholate and ursodeoxycholate were about 33, 45 and 4%, respectively, in the control and pre-treatment groups. In the post-treatment group, a markedly low value was observed in primary bile acids both glycine-conjugates and taurine-conjugates, especially in cholate, with a significantly high value of ursodeoxycholate (p<0.001) of both conjugates. On the other hand, no difference was observed in the composition of deoxycholate with significantly low percentage of taurine-conjugates compared with that in the pre-treatment group. The ratio of glycine-to taurine-conjugated bile acids showed a significantly higher value in the post-treatment group than in the pretreatment group (p <0.001) and the control group (p<0.005). The bile specimens were measured concomitantly by gas-liquid chromatography and the results were compared with those of high-performance liquid chromatography. The mean value of total bile acids, the ratio of cholate to chenodeoxycholate and the ratio of glycine-to taurine-conjugated bile acids obtained by the former analysis procedure represented about 57, 80 and 115% of those of the latter. It is concluded that the high G/T value seems to have a role in the dissolution mechanism. bile acid; ursodeoxycholic acid; cholesterol gallstone; high-performance liquid chromatography; ratio of glycine-to taurine-conjugated bile acids (G/ T ratio)Since the dissolution of cholesterol gallstones by chenodeoxycholic acid (CDCA) (Bell et al. 1972;Danzinger et al. 1972) and ursodeoxycholic acid (UDCA) (Sugata and Shimizu 1974;Makino et al. 1975) was demonstrated, an attention has been

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Chenotherapy for Gallstone Dissolution

Hofmann¹

1978

JAMA

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Changes in bile saturation and biliary bile acid composition in patients with gallstones who received chenodeoxycholic ("chenic") acid, cholic acid, or placebo were measured. Chenodeoxycholic induced bile desaturation; this effect was attributable solely to a decrease in the proportion of cholesterol. By gas chromatography, chenodeoxycholic acid increased substantially in the biliary bile acids of patients receiving it, and by mass spectrometry, no unusual bile acids were detected in appreciable amounts. Changes in bile saturation and biliary bile acid composition were then related to chenodeoxycholic acid dosage, and all of these variables were, in turn, related to gallstone response. In general, patients whose gallstones dissolved ingested a higher dose of chenodeoxycholic acid or had bile that contained a higher proportion of this acid and it was more unsaturated, but there were many exceptions, casting doubt on the value of a single analysis of fasting-state bile for predicting gallstone dissolutions. The major factor influencing response, provided dosage is adequate, appears to be gallstone type. Nonetheless, the proportion of chenodeoxycholic acid in biliary bile acids can probably be used to infer patient compliance.

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Effect of Oral Chenodeoxycholic Acid on Bile Acid Kinetics and Biliary Lipid Composition in Women with Cholelithiasis

Cited by 200 publications

References 33 publications

Bile Acid Kinetics in Relation to Sex, Serum Lipids, Body Weights, and Gallbladder Disease in Patients with Various Types of Hyperlipoproteinemia

Bile Acid Kinetics in Relation to Sex, Serum Lipids, Body Weights, and Gallbladder Disease in Patients with Various Types of Hyperlipoproteinemia

The effect of ursodeoxycholic acid on biliary bile acid composition in patients with cholesterol gallstone.

Chenotherapy for Gallstone Dissolution

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