Serum concentration of 27‐hydroxycholesterol predicts the effects of high‐cholesterol diet on plasma LDL cholesterol level

Abstract

The effect of dietary cholesterol on plasma cholesterol concentrations varies widely among individuals. Recent studies suggest that the synthesis of oxysterols is up-regulated when tissue cholesterol is saturated. The present study was undertaken to test the hypothesis that a serum high concentration of 27-hydroxycholesterol, one of the oxysterols, reflects positive cholesterol balance in the body and predicts intolerance to a high-cholesterol diet. In 30 subjects, 750 mg/day of cholesterol was added for 4 weeks to the ordinary diet. Blood samples were collected at the start and finish of the supplementation. Serum sterol and oxysterol concentrations were measured by high-resolution GC-MS. A receiver operating characteristic curve was drawn and the cutoff point (80 ng/mg cholesterol) was chosen to maximize sensitivity (81.3%) and specificity (64.3%) for predicting a positive change of LDL cholesterol concentration after cholesterol loading. Subjects with higher serum 27-hydroxycholesterol concentrations (>/= 80 ng/mg cholesterol) showed significantly (P < 0.05) high values for the change of LDL cholesterol concentration (+7.4 +/- 3.4%, mean +/- SEM, n = 17) compared with those with lower 27-hydroxycholesterol levels (-5.3 +/- 2.7%, n = 13). In subjects with high serum 27-hydroxycholesterol concentrations were unable to adapt to a high-cholesterol diet. The concentration of serum 27-hydroxycholesterol appears to reflect cholesterol saturation in the body and predicts to some extent a responsiveness to dietary cholesterol.