Abnormal bile acid absorption in familial hypertriglyceridemia

To better define the abnormality of bile acid metabolism associated with hypertriglyceridemia, we measured bile acid kinetics and absorption as well as preferential use of newly synthesized cholesterol for bile acid synthesis in eleven control and ten subjects with hypertriglyceridemia, six of whom could be classified as having familial hypertriglyceridemia (FHT). Fractional turnover rates of cholic acid and chenodeoxycholic acid were both significantly elevated in hypertriglyceridemic subject to nearly twice the rates in controls. Bile acid synthesis wits also significantly higher in hypertriglyceridemic subjects while bile acid pools were either unchanged or somewhat reduced. Consistent with these kinetics, bile acid absorption was significantly lower in hypertriglyceridemic subjects than in controls. Overall only 10-12% of bile acid was derived from newly synthesized cholesterol, and hypertriglyceridemic subjects did not differ from controls. Because hypertriglyceridemia should not alter bile acid absorption, these results are consistent with the previously suggested possibility (B. Angelin, K. S. Hershon, and J. D. Brunzell, 1987. Proc. Natl. Acad. Sci. USA. 84: 5434-5438) that impaired bile acid absorption may be a primary defect in some patients with hypertriglyceridemia.