Daniel G. Miller

Changes in Serum Bile Acids in Normal Human Subjects following the Adoption of a Low-Fat Diet

Dietary fat and bile acids have been implicated in the etiology of colon cancer.’S2 The mechanism by which these factors are involved in the etiology of this disease is unclear. In an effort to examine the effect of dietary fat on bile acid metabolism, we measured serum bile acids in fasting normal subjects (n = 12) before and three months following the adoption of a low-fat diet. Seven men and five women changed their diet from an average of 33% calories from fat to an average of 22% calories from fat, for a period of three months. Dietary fat was assessed from food records taken before the dietary change and at the end of the study period. The reduction in fat was achieved primarily by increasing carbohydrate. Blood samples were taken for bile acid measurements using a gas-chromatographic te~hnique.~ The following bile acids were identified and measured: lithocholic (LCA), deoxycholic (DCA), cholic (CA), chenodeoxycholic (CDCA), ursodeoxycholic (UDCA), and 7-ketolithocholic acid (7-KLCA). No significant differences were found in the total amounts of serum bile acids. A compositional change in the bile acids was observed. A comparison of the percentage of individual bile acids at baseline versus three months on a low-fat diet indicated a statistically significant increase in CDCA (14.9 f 5.0% to 24.4 2 18.6%, p < 0.001) and a reduction in UDCA (17.9 f 7.6% to 13.2 2 6.6%, p < 0.01); see FIGURE 1. In two subjects, 7-KLCA was present at low levels before the reduced fat diet, but became unmeasurable after three months on the diet. In the other subjects, 7-KLCA was not measurable before or after the diet period. In all subjects, an increase in the ratio of CDCAKJDCA was consistently observed. The observed changes in serum bile acids can be interpreted as resulting from a reduction in the 7a-hydroxysteroid dehydrogenase activity of intestinal bacteria. As shown in FIGURE^, intestinal bacteria are involved in the conversion of CDCA to UDCA. In this conversion, 7-KLCA is an obligatory intermediate (7-KLCA is formed by 7a-hydroxysteroid dehydrogenase from CDCA). An inhibition of 7a-hydroxysteroid dehydrogenase activity is expected to reduce the formation of 7-KLCA and consequently

Effect of a Low-Fat Diet on Estrogen and Bile Acid Metabolism in Normal Human Subjects

The urinary estrogen metabolites, 2-hydroxyestrone (2-OHE1) and 16α-hydroxyestrone (l6α-OHE1), as well as serum testosterone (T), estradiol (E2), and bile acids were measured in fasting normal subjects (n = 12) before and three months after the adoption of a low-fat diet (initial fat content ca. 40% reduced to ca. 20%). The serum bile acids measured were lithocholic (LCA), deoxycholic (DCA), cholic (CA), chenodeoxycholic (CDCA), and ursodeoxycholic acids (UDCA). No significant differences were found in the absolute or relative ratios for 2-OHE1, 16α-OHE1 E2, or T. The composition of the serum bile acids was changed; comparison of the percentage of each plasma bile acid at baseline with that after three months on the diet indicated an increase in CDCA (14.9% to 24.4%; p < 0.001) and a reduction in UDCA (17.9% to 13.2%; p < 0.01). A marked change in the ratio of CDCA/UDCA was also observed; the ratios of the three-month values compared with baseline were consistently increased by the diet (mean 2.72; SEM ±0.71). Only modest or no differences were observed with the ratios for the other bile acids. Because of the product-precursor relationship between CDCA and UDCA, these data can be interpreted as an indication of a dietary change in bile acid metabolism which resulted in inhibition of the oxidation at the 7-hydroxy group of CDCA and epimerization to UDCA.