Chenodeoxycholic acid inhibits increased cholesterol and cholestanol synthesis in patients with cerebrotendinous Xanthomatosis

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Abstract

The effects of chenodeoxycholic acid on cholesterol and cholestanol biosynthesis were evaluated in two subjects with CTX by isotope kinetic techniques and in one subject by hepatic enzyme analysis. Sterol specific activity decay curves conformed to two-pool models after intravenous pulse-labeling with [4-14C]cholesterol and [1,2-3H]cholestanol before and during treatment with CDCA. Calculations of daily production rates and the size of the rapidly exchangeable kinetic pools of cholesterol and cholestanol were compared during both periods. Since diets contained no cholestanol and were low in cholesterol, production rates approximated daily synthesis.

During CDCA treatment, average cholestanol synthesis decreased from 53 to 14 mg/day, and average cholesterol synthesis was reduced from 1036 to 434 mg/day. In one CTX subject, the hepatic activity of HMG-CoA reductase, the rate-determining enzyme for cholesterol biosynthesis, declined 54% after 7 days of bile acid treatment.

These data indicate that CDCA suppressed elevated cholesterol and cholestanol synthesis in CTX, and suggest that this primary bile acid may be useful in preventing the clinical progression of this disease.

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